Phaffia rhodozyma

Phaffia rhodozyma

Identity and Nomenclature

Phaffia rhodozyma is an orange-red pigmented basidiomycetous yeast that occupies a unique position in mycology as the only fungal species known to biosynthesize astaxanthin as its principal carotenoid. The genus Phaffia is an orange-colored basidiomycetous yeast genus of the order Cystofilobasidiales. It is an unusual heterobasidiomycetous yeast as it is the only yeast or fungus capable of synthesizing astaxanthin (ASX), a highly valuable carotenoid pigment with powerful antioxidant properties.

The organism carries two accepted scientific names reflecting its anamorphic and teleomorphic states. The asexual (anamorphic) form is designated Phaffia rhodozyma, while the sexual (teleomorphic) form is Xanthophyllomyces dendrorhous; this yeast has been found in tree exudates in the Northern Hemisphere at high altitudes and latitudes. It represents the teleomorphic state most commonly used for the production of the xanthophyll astaxanthin. In the current mycological literature both names remain in use, often interchangeably, depending on whether the context concerns the asexual culture form or the sexually reproducing state.

In terms of formal taxonomy, the basidiomycetous red yeast Xanthophyllomyces dendrorhous (asexual state Phaffia rhodozyma) belongs to a basal lineage of the Agaricomycotina within the Tremellomycetes. Red yeasts are classified in the Phylum Basidiomycota within two different orders, Sporidiobolales and Cystofilobasidiales; the Cystofilobasidiales can be mainly attributed to a single genus, Phaffia.

The active compound of primary interest is astaxanthin, whose full IUPAC-derived chemical designation is 3,3′-dihydroxy-β,β-carotene-4′-dione. Astaxanthin is more fully denoted as 3,3′-dihydroxy-β,β-carotene-4,4′-dione (C₄₀H₅₂O₄) and has been studied as a promising candidate compound for use as a fine chemical in food, pharmaceuticals, and cosmetics because of its antioxidant properties.

The stereochemistry of astaxanthin produced by P. rhodozyma is noteworthy. The astaxanthin produced by X. dendrorhous has (3R, 3′R) stereochemistry. Astaxanthin is a xanthophyll carotenoid with three possible stereoisomers: 3S, 3′S; 3S, 3′R (meso); and 3R, 3′R. The (3R, 3R′) isomer produced by P. rhodozyma is considered more readily digested than the (3S, 3S′) isomer, indicating that this yeast may be an advantageous astaxanthin bioresource.

Natural Habitat and Ecological Distribution

Phaffia rhodozyma was originally discovered in the slimy exudates of Betula spp. and a few other deciduous trees in the Northern Hemisphere. The yeast was originally isolated in the late 1960s by Phaff and collaborators, who collected strains from various broad-leafed trees in mountainous regions of Japan and Alaska. These strains had a red to orange color and could ferment glucose and produce amyloid compounds.

This basidiomycetous yeast was later formally described as Phaffia rhodozyma, and 67 additional strains were isolated from spring sap flows of Betula verrucosa in Russia. It is psychro-tolerant, originally isolated from trees in mountainous regions of Japan and Alaska, and has since been isolated from locations all over the world, including Antarctica.

Isolates of X. dendrorhous have also been recovered from the Southern Hemisphere (Patagonia, Argentina), where they were associated with fruiting bodies of Cyttaria hariotii, an ascomycetous parasite of Nothofagus trees. Comparison of internal transcribed spacer (ITS)-based phylogenies of P. rhodozyma and its tree host (Betulaceae, Corneaceae, Fagaceae, and Nothofagaceae) found them to be generally concordant, suggesting that different yeast lineages colonize different trees.

Within the cell, the yeast is best known for producing industrial amounts of the carotenoid astaxanthin; carotenoids are produced in X. dendrorhous to survive stressful environmental conditions, such as high UV exposure, oxidative stress from antimicrobials produced by its host tree, or plant pathogens. P. rhodozyma cells accrue astaxanthin and gain an intense red-pink coloration when faced with stressful conditions such as nutrient limitations (e.g., nitrogen or copper), the presence of toxic substances (e.g., antimycin A), or mutations in genes involved in nitrogen metabolism or respiration; since cellular accrual of astaxanthin occurs under a wide variety of conditions, this yeast represents a valuable model for studying oxidative stress in yeast cells.

Taxonomic History

Phaffia rhodozyma was tentatively described under the name Rhodozyma montanae by Phaff et al. (1972); this binomial was a nomen nudum, because a Latin description was not provided. M.W. Miller et al. (1976) renamed the yeast Phaffia rhodozyma with a Latin diagnosis and additional descriptive physiological and morphological properties. Golubev (1995) proposed that P. rhodozyma is the anamorphic state of Xanthophyllomyces and a synonym of Rhodomyces dendrorhous, a yeast superficially described by Ludwig (1891, 1896).

Common Preparations and Commercial Forms

Phaffia rhodozyma is produced commercially through submerged fermentation and is available in several processed forms:

• Dried whole-cell yeast biomass: The fermented yeast is harvested and dried to yield a biomass containing astaxanthin in its cell-bound form.
• Cell-disrupted or hydrolyzed preparations: When fed to rainbow trout, the deposition of astaxanthin in the fish flesh was dependent on the proper preparation of yeast cells before their inclusion into the feed. No astaxanthin was nutritionally available from intact yeast; if P. rhodozyma was mechanically ruptured, its pigments were transferred to the flesh of rainbow trout, coloring it salmon-pink. The most efficient deposition of astaxanthin in trout occurred when the cell wall of P. rhodozyma was partially removed by enzymatic digestion.
• Extracted and purified astaxanthin: Astaxanthin is isolated and formulated into standardized capsules or softgels for nutraceutical use. The commercial product AstaFerm™ is an astaxanthin dietary supplement derived from the yeast Phaffia rhodozyma; apart from its coloring ability, it is also a strong antioxidative ingredient with health-promoting properties.
• Feed additive forms: Fermentation-derived P. rhodozyma biomass has a composition rich in astaxanthin, proteins, lipids, minerals, and unsaturated fatty acids, and complies with feed additive regulations established by the US Food and Drug Administration (FDA), the European Commission, and China's Ministry of Agriculture and Rural Affairs.

The feasibility of commercial production of P. rhodozyma biomass and astaxanthin has been demonstrated using synthetic media, alfalfa juice, molasses, and whey permeate in single culture, or synthetic media in mixed culture with Bacillus circulans. This yeast can utilize various sugars as the carbon source, grow rapidly with a short cultivation cycle, has easier culture conditions, realizes a high-density fermentation, needs less production space, and is generally recognized as safe (GRAS).

Historical and Traditional Use

Phaffia rhodozyma has no documented history of use in traditional human medicine or folk practice. Unlike many botanical supplements, it was identified as a distinct species only in the twentieth century and its applied use is entirely a product of modern food science and aquaculture biotechnology.

The astaxanthin-containing yeast Phaffia rhodozyma was first isolated in the early 1970s from exudates of deciduous trees in mountainous regions of Japan and Alaska. Following its formal description in 1976, researchers almost immediately recognized its commercial potential as a pigment source. Phaffia rhodozyma was first demonstrated to pigment salmonid fishes in 1977.

The red yeast Phaffia rhodozyma has possible application as a component of diets for use in aquaculture; its primary value lies in its content of astaxanthin, which is much higher (5–50 times) than that found in crustacean meals. Use of this yeast as a dietary supplement in salmonid and crustacean diets was explored by Eric A. Johnson and other researchers since the early 1980s. This early industrial and aquacultural use represents the foundational application of P. rhodozyma, from which all subsequent nutraceutical interest has developed.

Initially used solely as an ingredient in aquaculture feeds, astaxanthin applications have become diverse in the nutraceutical, cosmetics, food, and feed industries, due to its antioxidant activity together with UV-light protection and anti-inflammatory roles. The shift toward human-oriented nutraceutical applications therefore reflects a relatively recent development, beginning in earnest during the 1990s and 2000s.

Key Constituents and Active Compounds

Astaxanthin: The Principal Bioactive

Phaffia rhodozyma synthesizes astaxanthin as a primary carotenoid pigment and β-carotene (the precursor of astaxanthin) as a secondary abundant pigment; astaxanthin comprises approximately 70% of total pigment molecules in P. rhodozyma, and the cells can be used directly as a feed additive. The astaxanthin content of X. dendrorhous can reach 0.5% of cell mass, representing about 85% of the total carotenoid content.

Carotenoids are organic lipophilic yellow to orange and reddish pigments of terpenoid nature that are usually composed of eight isoprene units; this group of secondary metabolites includes carotenes and xanthophylls, which can be naturally obtained from photosynthetic organisms, some fungi, and bacteria.

Wild-type strains display lower astaxanthin concentrations. Strains of Phaffia rhodozyma currently available generally produce from 30 to 2,000 micrograms per gram of cell mass.

Secondary Carotenoids and Minor Constituents

Phaffia rhodozyma differs strikingly from other pigmented yeasts in two ways: it ferments glucose and other sugars, and synthesizes astaxanthin as its main carotenoid. Other pigmented yeasts of the genera Cryptococcus, Rhodotorula, Rhodosporidium, Sporidiobolus, and Sporobolomyces are strictly aerobic and synthesize β-carotene, γ-carotene, torulene, or torularhodin as their principal pigment. In addition to astaxanthin and β-carotene, minor intermediates of the biosynthetic pathway, including phoenicoxanthin and 3-hydroxyechinenone, are present at low concentrations in wild-type cells.

Nutritional Composition

The fermentation-derived biomass of P. rhodozyma is rich in astaxanthin, proteins, lipids, minerals, and unsaturated fatty acids. The yeast cell wall contains polysaccharides typical of basidiomycetous fungi, and the overall biomass can serve as a protein-containing substrate, though its primary commercial value lies in its carotenoid content.

Biosynthetic Pathway

Astaxanthin and ergosterol are isoprenoids belonging to the conserved mevalonate pathway in P. rhodozyma; all isoprenoid compounds are based on the C5 isoprene unit. In the initial step of the mevalonate pathway, two molecules of acetyl-CoA, which is also a substrate of the fatty acid synthesis pathway, undergo condensation to yield acetoacetyl-CoA, which is then converted to 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA).

In fungi, including X. dendrorhous, all isoprenoids are biosynthesized from the common precursor mevalonate via the terpene pathway; supplementation of mevalonate has been shown to be critical to increase astaxanthin content in X. dendrorhous.

Two key enzymes are of particular importance in directing flux toward astaxanthin. Eight genes related to dicyclic and monocyclic pathways in three different strains of P. rhodozyma have been analyzed; among these genes, CRTS and CRTYB showed the closest correlations with carotenoid and astaxanthin biosynthesis, respectively. After CRTYB knockout, astaxanthin was decreased to an undetectable level. The enzyme CrtS (astaxanthin synthase) performs the terminal oxidation steps that convert β-carotene through intermediate forms to astaxanthin, and this final step performed by CrtS is what sets P. rhodozyma apart from other carotenogenic yeasts.

Mechanisms of Action

Antioxidant Activity

Astaxanthin, as an orange-red carotenoid pigment, acts as a protective agent against oxidative damage to cells in vivo. Reactive oxygen species (ROS), which are generated in both biochemical and photochemical systems, can cause cell damage by oxidizing biomolecules such as DNA, protein, and lipids. Carotenoids in general are able to eliminate ROS or other free radical-containing species, and the antioxidant activity of astaxanthin is reported to be 100–500 times that of vitamin E.

Astaxanthin's antioxidative mechanisms are multifaceted. It directly scavenges free radicals such as superoxide anions, hydroxyl radicals, and singlet oxygen, and interrupts lipid peroxidation chains due to its conjugated double bond structure. Moreover, astaxanthin has been shown to activate the Nrf2 pathway, promoting the expression of endogenous antioxidant enzymes such as superoxide dismutase (SOD), catalase, and glutathione-peroxidase (GPx).

Anti-Inflammatory Mechanisms

Astaxanthin modulates redox-sensitive signaling pathways, including NF-κB, thereby reducing the expression of inflammatory mediators. Astaxanthin (3,3-dihydroxy-β,β-carotene-4,4′-dione) is a ketocarotenoid with antioxidant, anti-inflammatory, anti-aging, anti-tumour, and immune-enhancing properties.

Structural Basis for Bioactivity

The unique molecular structure of astaxanthin — with hydroxyl and keto groups at both ends of a polyene chain, and the polyene chain itself spanning the full length of the molecule — allows it to span the entire cell membrane bilayer, providing antioxidant protection on both the interior and exterior surfaces simultaneously, unlike shorter-chain antioxidants such as vitamin E. Its lipophilic nature enables distribution into lipid-rich tissues, membranes, and compartments.

Scientific Evidence by Health Area

Aquaculture, Animal Feed, and Pigmentation

The most extensively documented application of Phaffia rhodozyma-derived astaxanthin is as a feed additive in aquaculture and poultry production. The yeast is a potentially useful dietary supplement in salmonid and poultry feeds because of its high content of the carotenoid pigment astaxanthin; when hydrolyzed cells are added to the diet, astaxanthin is readily absorbed from the gut and effectively enhances the pink to orange color of the flesh of pen-reared salmonids.

A study in Penaeus monodon (black tiger shrimp) evaluated the effects of dietary astaxanthin from P. rhodozyma. The study investigated the effect of dietary astaxanthin from Phaffia rhodozyma on growth performance, survival, carotenoid content, antioxidant and immune-related enzyme activity, intestinal microbiota, and disease resistance against Vibrio parahaemolyticus in Penaeus monodon; juveniles were fed experimental diets supplemented with 0, 20.5, 41, 61.5, 82, and 102.5 mg/kg of astaxanthin in triplicate for 56 days. Shrimp fed with astaxanthin supplementation significantly improved growth performance compared with the control, and significantly increased survival and decreased feed conversion ratio (FCR) demonstrated the beneficial effects of dietary astaxanthin. Dietary increasing astaxanthin levels significantly increased shrimp resistance performance to V. parahaemolyticus, which may have been caused by increased total carotenoid contents in shrimp tissues from all the astaxanthin-supplemented treatments.

A comparative study evaluated astaxanthin from three sources — synthetic astaxanthin (SA), Haematococcus pluvialis (HP), and Phaffia rhodozyma (PR) — in juvenile Pacific white shrimp Litopenaeus vannamei. This study evaluated the effects of dietary SA, HP, and PR on growth performance, antioxidant activity, innate immunity, morphology, and pigmentation; shrimp were fed with control diet and astaxanthin diets containing 20 mg/kg of astaxanthin from three sources for 56 days. Growth performance was observably elevated in the HP and PR groups compared with the control; the astaxanthin-supplemented diets markedly elevated the activities of glutathione peroxidase (GPx) and GST in the intestine and hepatopancreas while observably reducing MDA content; and the apoptosis rates in three astaxanthin groups were noticeably reduced compared with the control group.

Evidence strength (aquaculture/animal):strong — Multiple controlled studies across species demonstrate consistent beneficial effects on pigmentation, growth, antioxidant status, and immune parameters in farmed fish and crustaceans when fed P. rhodozyma-derived astaxanthin. The evidence base here is the most robust of any area associated with this organism.

Antioxidant Effects in Humans

Astaxanthin is a natural C40 carotenoid with numerous reported biological functions, most of them associated with its antioxidant and anti-inflammatory activity, standing out from other antioxidants as it has shown the highest oxygen radical absorbance capacity (ORAC), 100–500 times higher than α-tocopherol and a 10-times higher free radical inhibitory activity than related antioxidants including α-tocopherol, α-carotene, β-carotene, lutein, and lycopene.

Human trials report reductions in oxidative stress biomarkers such as malondialdehyde and lipid hydroperoxides, alongside increases in endogenous antioxidant defenses including superoxide dismutase. A 2025 systematic review including 15 human studies found that astaxanthin consistently reduced pro-inflammatory cytokines (IL-6, TNF-α, TGF-β1) and oxidative stress indices while increasing antioxidant capacity (SOD, TAC). Astaxanthin demonstrates broad antioxidant and anti-inflammatory properties, supporting its role as a promising adjunctive therapy for metabolic, reproductive, and cardiovascular health; however, further well-designed clinical trials are needed to confirm optimal dosing and mechanisms of action.

Evidence strength (human antioxidant biomarkers):moderate — Multiple small-to-medium human studies consistently show reductions in oxidative stress markers, but most trials are short, limited in participant numbers, and often use astaxanthin derived from H. pluvialis rather than P. rhodozyma specifically.

Skin Aging and Photoprotection

A systematic review and meta-analysis published in 2021 (PMC8472736) analyzed eleven human studies on oral and/or topical astaxanthin and skin aging parameters. A comprehensive search of PubMed, Scopus, and Web of Science found eleven studies; nine randomized, controlled human studies assessed oral astaxanthin effects, and two open-label, prospective studies evaluated topical or oral-topical effects on skin aging. Oral astaxanthin supplementation significantly restored moisture content (SMD = 0.53; 95% CI = 0.05, 1.01; I² = 52%; p = 0.03) and improved elasticity (SMD = 0.77; 95% CI = 0.19, 1.35; I² = 75%; p = 0.009) but did not significantly decrease wrinkle depth (SMD = −0.26; 95% CI = −0.58, 0.06; I² = 0%; p = 0.11) compared to placebo. The authors concluded that ingestion and/or topical usage of astaxanthin may be effective in reducing skin aging and has promising cosmetical potential, as it improves moisture content and elasticity and reduces wrinkles.

A separate 2025 systematic review and meta-analysis of randomized controlled trials examining dietary supplements for skin photoaging found that three studies (n = 102) investigated the effects of astaxanthin with dosages ranging from 2 to 4 mg, all administered in capsule form; however, this meta-analysis found that carotenoids did not show any significant benefits in improving skin photoaging or measures of skin elasticity. The authors noted that due to inconsistent findings and limited research, the effects of dietary supplements on skin photoaging could not be determined in randomized controlled trials with two or fewer studies.

Evidence strength (skin):preliminary to moderate — Meta-analytic data on moisture and elasticity parameters show significant effects, but sample sizes are small, heterogeneity is moderate-to-high, and evidence on photoprotection specifically is insufficient and inconsistent.

Cardiovascular Health

Astaxanthin is a xanthophyll carotenoid with potent antioxidant and anti-inflammatory effects demonstrated in both experimental and human studies; oxidative stress and inflammation are common pathophysiological features of atherosclerotic cardiovascular disease, hence astaxanthin may have a potential therapeutic role in this condition.

Astaxanthin supplementation in randomized controlled trials (RCTs) has been shown to significantly reduce inflammatory markers and lipid profiles, improve endothelial function, and alleviate symptoms of heart failure, highlighting its therapeutic potential. Several studies have shown that astaxanthin can improve cholesterol removal from macrophages, decrease plaque buildup, and enhance lipid profiles by lowering triglycerides and increasing high-density lipoprotein (HDL) cholesterol levels.

A randomized, double-blind, placebo-controlled trial in patients with coronary artery disease (CAD) was conducted: this trial was conducted among 50 CAD patients; participants were randomly allocated into two groups to intake either astaxanthin supplements (12 mg/day) or placebo for 8 weeks.

Regarding early safety and bioavailability studies, Iwamoto et al. (2000) tested different doses (1.8, 3.6, 14.4, 21.6 mg/day) over 2 weeks and found inhibition of LDL oxidation.

Limited, short-duration, and small sample size studies have assessed the effects of astaxanthin on oxidative stress and inflammation biomarkers and have investigated bioavailability and safety; so far no significant adverse events have been observed, and biomarkers of oxidative stress and inflammation are attenuated with astaxanthin supplementation. Human clinical cardiovascular studies using astaxanthin therapy as a primary endpoint have not yet been fully reported.

Evidence strength (cardiovascular):preliminary — Preclinical data is mechanistically coherent and promising. Human trials have demonstrated improvements in surrogate biomarkers (LDL oxidation, lipid profiles), but there are no completed large-scale cardiovascular outcomes trials specifically testing P. rhodozyma-derived astaxanthin.

Exercise Performance and Muscle Recovery

A randomized double-blind placebo-controlled trial assessed the effect of astaxanthin on muscle soreness following eccentric exercise. The purpose was to investigate the effect of a four-week course of astaxanthin supplementation at 12 mg/day on subjective markers of DOMS, recovery, and performance after a bout of muscle-damaging eccentric exercise; nineteen resistance-trained men completed a between-group design with a four-week supplementation period of 12 mg/day of either astaxanthin or placebo.

Another randomized double-blind placebo-controlled trial examined exercise recovery and heat tolerance. Twenty-two male participants received either placebo (n = 10) or astaxanthin (n = 12) at 12 mg/day orally for 30 days, and were tested pre- and post-supplementation with a maximal oxygen uptake (VO₂ Max) test and a heat tolerance test (2-hour walk at 40°C, 40% relative humidity, 5 kph, 2% incline).

A systematic review and meta-analysis of trials in athletic men found that astaxanthin supplementation improved cycling time trial performance; the proposed mechanism is that intense exercise generates a surge of oxidative stress in muscle tissue, and astaxanthin's antioxidant activity may help buffer that damage, allowing muscles to sustain output longer. The evidence is still building in this area and most studies have been relatively small, but the direction of findings is consistent.

Evidence strength (exercise/muscle):preliminary — Individual randomized controlled trials and a meta-analysis suggest modest benefits for endurance performance and recovery markers, but study sizes are small, and the astaxanthin source in most trials is not specifically P. rhodozyma-derived.

Ocular Health

Preclinical and human pharmacokinetic data indicate that astaxanthin can cross the blood–brain barrier, supporting its potential role in neural protection. Because astaxanthin crosses the blood-retinal barrier, it reaches the eye tissues directly rather than relying on indirect antioxidant effects elsewhere in the body, giving it a plausible mechanism for reducing the oxidative stress that accumulates during long periods of screen use. Supplementation with astaxanthin (typically 4–9 mg/day) has been shown to improve markers of oxidative balance in ocular tissues and enhance visual performance in adults exposed to prolonged work at visual display terminals.

Evidence strength (eye health):preliminary — Small human studies report improvements in visual fatigue and oxidative markers in ocular tissues; no large RCTs have been conducted specifically for astaxanthin from P. rhodozyma in ocular disease outcomes.

Metabolic, Reproductive, and Other Areas

Combined astaxanthin and exercise interventions improved body composition, lipid profiles, insulin sensitivity, and immune recovery in human studies. In women with polycystic ovary syndrome (PCOS) or endometriosis, astaxanthin downregulated endoplasmic reticulum stress-related apoptotic pathways and improved oocyte and embryo quality. Cardiometabolic and respiratory outcomes also showed improved endothelial function and reduced disease severity.

Evidence for disease-modifying effects in neurodegenerative disorders remains preliminary, with current support derived mainly from animal models and small human trials.

Body Systems and Health Areas Associated with Phaffia rhodozyma / Astaxanthin

• Antioxidant/Redox system: Direct free radical scavenging; Nrf2 pathway activation; reduction of systemic oxidative stress markers (malondialdehyde, lipid hydroperoxides)
• Immune system: Reduction of pro-inflammatory cytokines (IL-6, TNF-α, TGF-β1); enhancement of immune enzyme activity in aquaculture studies
• Cardiovascular system: Inhibition of LDL oxidation; improvement in lipid profiles; potential endothelial protection
• Integumentary system (skin): Improvement in skin moisture content and elasticity; photoprotective antioxidant effects
• Musculoskeletal system: Reduction of exercise-induced oxidative damage and subjective muscle soreness
• Ocular system: Antioxidant protection of retinal tissue; improvement of visual performance markers under visual fatigue conditions
• Reproductive system: Improvement of sperm parameters in clinical studies; potential benefits in PCOS and endometriosis
• Nervous system: Ability to cross the blood–brain barrier suggests neuroprotective potential; currently supported only by preliminary evidence

Dosage Forms and Dosages Reported in Studies

The dosages reported in the scientific literature pertain principally to astaxanthin as the active compound, derived from Phaffia rhodozyma or other natural sources. The following dosages reflect those reported in specific cited studies:

• In a randomized controlled trial in renal transplant patients, 12 mg/day of astaxanthin was administered for one year.
• In a randomized double-blind placebo-controlled trial in coronary artery disease patients, 12 mg/day was administered for 8 weeks.
• In a randomized placebo-controlled trial in healthy males, 12 mg/day was given orally for 30 days.
• In a trial examining post-exercise muscle soreness in resistance-trained men, 12 mg/day was supplemented for four weeks.
• Spiller et al. (2003) demonstrated safety in humans at 6 mg/day (3 × 2 mg tablets/day) over 8 weeks.
• Iwamoto et al. (2000) tested doses of 1.8, 3.6, 14.4, and 21.6 mg/day over 2 weeks.
• Comhaire et al. (2005) used 16 mg/day for 12 weeks and reported improved sperm parameters.
• Studies investigating skin effects used dosages ranging from 2 to 4 mg, administered in capsule form.
• In aquaculture (shrimp): experimental diets with astaxanthin from P. rhodozyma at levels of 0, 30, 60, and 90 mg/kg were fed to Litopenaeus vannamei for 8 weeks.
• In pharmacokinetic study: a pharmacokinetics profile study of AstaFerm™ (a P. rhodozyma-derived astaxanthin supplement) was conducted in 12 healthy male adults who received a single dose in a single-center, open-label, non-randomized study.

Clinical studies involving more than 2,000 participants report good tolerability at supplemental doses of 4–12 mg/day for periods up to one year, with no serious adverse effects observed.

Regulatory Status

The FDA has approved astaxanthin as a color additive for fish feed, while the European Commission has established a maximum daily dose of 8 mg for dietary supplements. The yeast Xanthophyllomyces dendrorhous is considered by EFSA to be suitable for the qualified presumption of safety (QPS) approach to safety assessment; therefore, the use of the production strain in the production of the additive would not raise any safety concern for the target species, the consumers of products from animals fed the additive, and the environment.

Astaxanthin-rich Phaffia rhodozyma (ATCC SD-5340) was provisionally authorized for use in salmon and trout feed in the European Union. A conclusion was reached that Phaffia rhodozyma yeast is "Generally Recognized As Safe (GRAS)" as an ingredient in feed for salmonids according to US regulatory assessments, with the proviso that the yeast is killed during processing.

Safety Considerations and Interactions

General Tolerability

The safety, bioavailability, and effects of astaxanthin on oxidative stress and inflammation have been assessed in a small number of clinical studies; no adverse events have been reported and there is evidence of a reduction in biomarkers of oxidative stress and inflammation with astaxanthin administration.

The EFSA considers the combined intake of up to 8 mg/day of astaxanthin from diet and supplements to be safe for adults, corresponding to an acceptable daily intake of 0.2 mg/kg body weight. Clinical studies involving more than 2,000 participants report good tolerability at supplemental doses of 4–12 mg/day for periods up to one year, with no serious adverse effects observed.

Occupational/Worker Safety

The EFSA FEEDAP Panel concluded that the additive is irritant to skin and eyes, and a skin and respiratory sensitizer, although exposure by inhalation is likely low. This consideration applies primarily to workers in production and processing facilities handling dried yeast biomass as a bulk material, rather than to consumers of finished supplement products.

Populations with Insufficient Safety Data

Available data do not indicate safety concerns for healthy adults; however, evidence is insufficient for pregnancy, lactation, and pediatric use.

Drug Interactions

Caution is advised for individuals using antihypertensive, anticoagulant, or antidiabetic medications due to potential additive physiological effects. These interactions are based on astaxanthin's known pharmacological activities (blood pressure reduction, antidiabetic effects, antiplatelet-like activity) and have not been formally characterized in dedicated drug interaction trials.

Immunosuppressant Context

In the context of organ transplant recipients on immunosuppressive therapy, the high incidence of atherosclerosis in such patients is related to increased arterial stiffness, vascular dysfunction, elevated oxidative stress, and inflammation associated with immunosuppressive therapy; astaxanthin has shown promise as an antioxidant and anti-inflammatory therapeutic agent and was investigated as a potential intervention in this population.

Skin Coloration

At supplemental doses used in human studies, astaxanthin may impart a subtle orange tint to skin at high doses, consistent with its xanthophyll nature, though this is not reported as an adverse effect at the doses (4–12 mg/day) typically studied.

Production Strain-Specific Considerations

Phaffia rhodozyma products marketed for feed use are manufactured using pure culture techniques that abide by GMP standards; traditionally developed strains have been produced by traditional chemical mutagenesis and selection and have not been subjected to recombinant DNA techniques or protoplast fusions, and the product does not contain introduced antibiotic resistance genes or other foreign DNA sequences. However, some commercially developed strains are the product of genetic engineering, which may affect regulatory classification in certain jurisdictions.

Research Gaps and Current Limitations

The scientific literature on Phaffia rhodozyma and its astaxanthin as a human nutraceutical shares several consistent limitations that temper the translation of findings to clinical recommendations:

• The overwhelming majority of well-controlled human clinical trials have used astaxanthin derived from Haematococcus pluvialis, not Phaffia rhodozyma. Given the different stereochemistry of the astaxanthin produced by P. rhodozyma (predominantly 3R,3R′ vs. the 3S,3S′ form found in H. pluvialis), extrapolation between sources should be made cautiously.
• Further well-designed clinical trials are needed to confirm optimal dosing and mechanisms of action.
• Human clinical cardiovascular studies using astaxanthin therapy as a primary endpoint have not yet been reported.
• Most human trials are small (fewer than 100 participants), short in duration (8–16 weeks), and often industry-sponsored, limiting the strength of conclusions that can be drawn.
• Although astaxanthin has emerged as the second most popular carotenoid, with global market sales estimated at US$186 million in 2023 and projected to reach US$742 million by 2031, synthetic astaxanthin currently dominates the market owing to its cost-effectiveness, whereas natural astaxanthin demonstrates superior bioavailability and antioxidant activity.

References

• The Untapped Australasian Diversity of Astaxanthin-Producing Yeasts — PMC (2020)
• Biogeography, Host Specificity, and Molecular Phylogeny of Phaffia rhodozyma and Xanthophyllomyces dendrorhous — PMC / Applied and Environmental Microbiology (2007)
• Deciphering the mechanism by which Phaffia rhodozyma responds to environmental, nutritional, and genetic cues — Journal of Industrial Microbiology and Biotechnology (2021)
• Biosynthesis of Astaxanthin as a Main Carotenoid in Xanthophyllomyces dendrorhous — PMC (2017)
• Astaxanthin biosynthesis is enhanced by high carotenogenic gene expression in a Phaffia rhodozyma mutant strain — FEMS Yeast Research (2011)
• Overexpression of a bifunctional enzyme, CrtS, enhances astaxanthin synthesis through two pathways in Phaffia rhodozyma — PMC / Microbial Cell Factories (2015)
• Phaffia rhodozyma as an astaxanthin source in salmonid diets — Aquaculture (1980)
• Effects of Dietary Phaffia rhodozyma Astaxanthin on Growth Performance, Immune-Physiological Parameters, and Disease Resistance in Penaeus monodon — PMC / Frontiers in Microbiology (2021)
• Dietary Synthetic and Natural Astaxanthin from Haematococcus pluvialis and Phaffia rhodozyma Improves Growth, Antioxidant Capacity, and Innate Immunity in Litopenaeus vannamei — PMC (2025)
• Dietary Phaffia rhodozyma-Synthesized 3S,3′S-Astaxanthin Promotes Body Coloration and Muscle Quality in Litopenaeus vannamei — PMC / Aquaculture Nutrition (2025)
• The Role of Astaxanthin as an Antioxidant and Anti-Inflammatory Agent in Human Health: A Systematic Review — PMC (2025)
• Systematic Review and Meta-Analysis on the Effects of Astaxanthin on Human Skin Ageing — PMC (2021)
• Effectiveness of Dietary Supplements for Skin Photoaging in Healthy Adults: Systematic Review and Meta-Analysis — Frontiers in Medicine (2025)
• Astaxanthin in Cardiovascular Health and Disease — Molecules / PMC (2012)
• Astaxanthin: A Potential Therapeutic Agent in Cardiovascular Disease — PMC (2011)
• Effects of Astaxanthin Supplementation on Metabolic Parameters and TNF-α in Coronary Artery Disease Patients: RCT — Frontiers in Nutrition (2023)
• Astaxanthin vs Placebo on Arterial Stiffness, Oxidative Stress and Inflammation in Renal Transplant Patients (Xanthin): RCT Protocol — PMC / BMC Nephrology (2008)
• Astaxanthin Improves Aerobic Exercise Recovery Without Affecting Heat Tolerance in Humans — PMC (2020)
• Astaxanthin Supplementation Reduces Subjective Markers of Muscle Soreness following Eccentric Exercise — PMC (2025)
• Safety and efficacy of a feed additive consisting of astaxanthin-rich Phaffia rhodozyma for salmon and trout — EFSA Journal (2022)
• Safety and efficacy of astaxanthin-rich Phaffia rhodozyma for salmon and trout (Igene Biotechnology) — PMC / EFSA Journal (2022)
• Safety and Pharmacokinetics of Phaffia rhodozyma Astaxanthin (AstaFerm™) — ClinicalTrials.gov (NCT03807050)
• Advances and trends for astaxanthin synthesis in Phaffia rhodozyma — Microbial Cell Factories / Springer (2025)
• Stress-induced astaxanthin biosynthesis in Phaffia rhodozyma: Bridging mechanistic understanding to industrial feasibility — ScienceDirect (2025)
• Astaxanthin in Liver Health and Disease: A Potential Therapeutic Agent — PMC (2020)
• From nutrition to therapeutics: the diverse inflammopharmacological and biomedical roles of astaxanthin — PMC (2025)
• GRAS Status of Phaffia rhodozyma Yeast as a Feed Ingredient — FDA/Regulations.gov