IngredientsDunaliella salina (Dunal) Teodoresco is a unicellular green alga found in environments with high salt concentration, classified within the domain Eukaryota, kingdom Viridiplantae, phylum Chlorophyta, class Chlorophyceae, order Volvocales, and family Dunaliellaceae. It bears two flagella of equal length inserted at the anterior of the cell body, which is usually ovoid in shape but can vary with growth conditions; the cell lacks a rigid cell wall but is covered with a glycocalyx-type mucilage.
Michel Félix Dunal first described the organism in 1838 in the south of France, but it was not formally named until 1905 by Teodoresco. As of the time of current research, 27 Dunaliella species have been identified, with 23 species found in marine and hypersaline environments and 4 in freshwater or brackish waters. The species is also encountered in the scientific literature under the synonymous designation Dunaliella bardawil (Ben-Amotz & Avron), a strain-level designation sometimes applied to especially high-carotenoid-accumulating isolates.
Dunaliella species are able to tolerate varying NaCl concentrations, ranging from 0.2% to approximately 35%, making D. salina a hyper-halotolerant organism found in high densities in saline lakes. It can grow normally at NaCl concentrations ranging from 0.05 M to saturation, regulating osmotic pressure inside and outside the cell by regulating glycerol metabolism. The halophilic strains produce considerable amounts of β-carotene, an antioxidant with significant commercial value, and they thrive at salinities of 6–12%, regulating osmotic pressure by accumulating glycerol, which promotes the production of valuable compounds such as lipids and carotenoids.
The single large, cup-shaped chloroplast can hold large amounts of β-carotene, which makes it appear orange-red; this β-carotene appears to protect the organism from long-term UV radiation to which D. salina is exposed in its typical environments.
Natural β-carotene derived from D. salina is marketed in various forms: β-carotene extracts, Dunaliella powder for human use, and dried Dunaliella for feed coloration. Large commercial plants produce "natural" β-carotene in the form of suspensions in oil, beadlets, and water-soluble powder for pharmaceutical and nutraceutical applications. Whole-cell dried biomass powders (ranging from green to orange in color depending on carotenoid loading) and oleoresin softgel capsules standardized to a set quantity of natural β-carotene are the predominant dietary supplement forms encountered in commerce.
Throughout the 1800s, after its first recorded discovery, a number of other biologists independently discovered this form of algae in various locations across Europe and North Africa (including Algiers). In the early 1900s, even without advanced technology, scientists recognized that Dunaliella contained β-carotene and thus had potential commercial value as a food or nutritional supplement.
Dunaliella salina was first proposed as a commercial source of β-carotene by Massyuk in 1966 and later as a source of glycerol by Ben-Amotz and colleagues in 1982. β-Carotene from Dunaliella is now being produced on a commercial scale in Australia, the USA, and Israel, with pilot-scale projects having been undertaken in China, Chile, Spain, and Kuwait.
The recognition that some species of Dunaliella, particularly D. salina and D. parva, accumulate very high concentrations of the carotenoid β-carotene when grown in high salinities and high light led to the development of large-scale cultures as a commercial source of natural β-carotene beginning in the 1980s in Australia, Israel, and the USA. Almost all of the natural β-carotene is currently produced by two large plants each with over 740 ha of pond area, at Hutt Lagoon in Western Australia and at Whyalla in South Australia, with smaller-scale production in Eilat, Israel.
For a long time, the most common way to produce Dunaliella for commercial purposes was outdoor pools; Dunaliella manufacturing plants were built in hot and arid areas near suitable saltwater sources. Due to its tolerance to high salinity, contamination is reduced, and it can grow in open systems.
Dunaliella salina does not carry a documented traditional ethnobotanical use analogous to, for example, herbal medicinal plants with centuries-long records of organized preparation and administration. The organism was only formally identified and named in the 20th century. Its use as a dietary ingredient is essentially a product of 20th-century nutritional science and biotechnology. In recent decades there has been increasing interest in obtaining products from natural sources, including carotenoids; these compounds are among the bioactive products used for the purpose of producing functional foods, and they can be acquired from microalgae. The algal β-carotene is sold as an antioxidant for human health, a natural pigment for products such as margarine, and also for the pigmentation of farmed prawns.
Dunaliella salina can accumulate up to 25% of dry weight in lipids and is regarded as the most efficient natural source of β-carotene. Among various carotenoid-rich microalgae, D. salina has the greatest carotene concentration, making up approximately 10% of algal dry weight in high-carotenoid strains. On a commercial scale, D. salina has emerged as one of the most important species for the bioproduction of β-carotene, and it is expected to provide more than 95% of the overall requirement for this compound, with the ability to produce β-carotene from microalgae of the genus Dunaliella estimated at approximately 1,200 tons annually.
A defining feature that differentiates Dunaliella-derived β-carotene from the synthetic form is its isomeric composition. This β-carotene is composed of approximately 50% all-trans and 50% 9-cis β-carotene isomers. Natural β-carotene consists of two isomers — all-trans and 9-cis — whereas synthetic β-carotene contains only the all-trans isomer, which has lower liposolubility and lower antioxidant activity than the natural mixture. The 9-cis isomer of β-carotene is found naturally in vegetables and fruits but accumulates to the highest levels in the alga Dunaliella.
The β-carotene isomers in D. salina include all-trans-β-carotene and 9- or 9'-cis-β-carotene; the 9-cis isomer has demonstrated a higher antioxidant activity due to the higher reactivity of the cis bond compared to the trans bond.
In addition to chlorophyll A and B, members of D. salina species produce useful carotenoid pigments including carotene α and β, neoxanthin, violaxanthin, lutein, and zeaxanthin. In the cells, β-carotene is usually accompanied by other carotenoids such as astaxanthin and canthaxanthin, which are all accumulated in oily globules in the chloroplast.
The ability to grow at very high salinities is due to the cells accumulating glycerol as a compatible solute; glycerol is a 3-carbon polyol which is infinitely soluble, acts as the intracellular osmoticum balancing external osmotic activity, and protects the integrity of cell proteins. Attempts have been made to exploit the high concentrations of glycerol accumulated by D. salina as the basis for commercial production of this compound, but economic feasibility has been assessed as low and no major biotechnological operation exploiting the alga for glycerol production has been established.
D. salina contains many active substances including glycerol, β-carotene, proteins, and vitamins, and is used in the production of dried biomass or cell extracts for pharmaceutical formulations, food additives, and fine chemicals. Ethanol and hexane extracts of D. salina contain bioactive fatty acids including palmitic, α-linolenic, and oleic acids, which are major components of the extracts.
Carotenoids in the animal body improve the immune system, inhibit and prevent cancer, delay aging, improve liver damage, and act as nutritional antioxidants that promote communication between cellular junctions, thereby potentially inhibiting the occurrence of some chronic diseases. Among them, β-carotene is a vital precursor for the synthesis of vitamin A in humans and animals, and is also an antioxidant. In Dunaliella salina cells, β-carotene has a major protecting role for biomolecules when the production of reactive oxygen species is elevated.
β-Carotene, a tetraterpene synthesized from isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP), serves as a vital precursor to vitamin A, offering benefits including antioxidation, immune system support, reduction of cardiovascular disease risk, and cancer prevention. Conversion of β-carotene to retinol (vitamin A) occurs enzymatically in intestinal enterocytes; importantly, because the conversion is tightly regulated by vitamin A status, provitamin A from plant/algal sources does not produce the hypervitaminosis A risk associated with preformed retinol.
The three main functions of β-carotene are antioxidant effects, cell gap junction-related functions, and immune-related functions. Beyond antioxidant activity, β-carotene influences intracellular communication, immune responses, neoplastic transformation, and control of growth.
The content of carotenoids and omega-3 fatty acids in D. salina has antioxidant influences attributed to beneficial impacts on the activity of liver enzymes; this may be useful in avoiding oxidative stress that injures the liver by prompting glutathione synthesis. Research has suggested that D. salina extract has a hepatoprotective influence owing to the presence of carotenoids, which are recognized for their antioxidant activity, and that high doses of D. salina extract may trigger liver cell regeneration, limiting the leakage of hepatic enzymes into the blood.
Several pharmacokinetic studies in humans have investigated the absorption of the isomeric mixture from Dunaliella preparations.
The uptake of all-trans and 9-cis β-carotene and of α-carotene from a natural carotene preparation from Dunaliella salina (commercial product "Betatene") was studied in humans. All-trans β-carotene and α-carotene were absorbed well, with serum peak concentrations between 24 and 48 hours; however, 9-cis β-carotene was not detected in human serum even after repeated doses. This could be due to preferential absorption of all-trans β-carotene, rapid distribution of 9-cis β-carotene into the tissue, or the presence of isomerase activity processing 9-cis to all-trans β-carotene.
In a separate study, 24 human subjects were supplemented with 100 mg β-carotene/day for 6 days, either as synthetic all-trans β-carotene or a natural β-carotene preparation derived from Dunaliella salina consisting of a 50:50 mixture of all-trans and 9-cis isomers. This loading dose was followed by a 23-day maintenance phase. The loading dose resulted in significant increases in plasma concentrations of both isomers; the all-trans group showed a 7.2- and 5.0-fold increase in all-trans and 9-cis plasma concentrations, respectively, while the group receiving the 50:50 mixture showed a 4.0- and 3.7-fold increase in all-trans and 9-cis concentrations, respectively.
In a metabolic study using isotopically labeled 9-cis β-carotene administered as a single oral dose to three subjects, researchers found substantial concentrations of labeled all-trans β-carotene and all-trans retinol in plasma 5 hours after dosing, but very low concentrations of labeled cis β-carotene, indicating that absorbed 9-cis β-carotene is rapidly isomerized to all-trans forms in the body.
Evidence strength: The bioavailability studies are small in scale (3–24 participants) and relatively short in duration. They establish pharmacokinetic behavior but do not define clinically optimal dosing regimens for health outcomes.
Dunaliella-derived 9-cis β-carotene has been the subject of a series of clinical investigations for retinitis pigmentosa (RP), a hereditary degenerative retinal disease involving defects in the retinoid cycle.
A clinical trial titled "Treatment with 9-cis β-carotene-rich powder in patients with retinitis pigmentosa: a randomized crossover trial" was published in JAMA Ophthalmology in 2013 (Rotenstreich et al., JAMA Ophthalmol. 2013 Aug;131(8):985–92). Previous research published from that group showed that prolonged treatment (at least 3 months) with 9-cis β-carotene can lead to significant improvements in retinal function and substantial visual field changes in a subset of RP patients.
An ongoing registered clinical trial at Sheba Medical Center is designed as a randomized, double-masked, crossover, placebo-controlled study to evaluate the efficacy of a 9-cis β-carotene-rich Dunaliella supplement in patients with retinitis pigmentosa; the study specifically targets individuals with mutations in genes related to the retinoid cycle.
Valorisation of the efficacy of 9-cis β-carotene in treating atherosclerosis, psoriasis, and inhibiting atherogenesis and retinitis pigmentosa is considered increasingly urgent, but supplies of 9-cis β-carotene are scarce and the compound is difficult to synthesize chemically, unlike the much more common all-trans form.
Evidence strength: There are peer-reviewed randomized controlled trials supporting a signal of benefit in a subset of RP patients with specific retinoid-cycle gene mutations. However, trials have been small and limited largely to specific mutation types; larger confirmatory trials are ongoing. Evidence cannot be generalized to RP patients without retinoid-cycle mutations.
A study by Shaish and colleagues (Atherosclerosis, 189(1):215–221, 2006) reported that 9-cis β-carotene-rich powder of the alga Dunaliella bardawil increased plasma HDL-cholesterol in fibrate-treated patients.
Researchers from this same group previously showed that a 9-cis β-carotene-enriched diet, provided as Dunaliella powder, has a beneficial effect on atherosclerosis and diabetes mellitus in animal models and on lipid profiles in human trials.
From a broader β-carotene supplementation perspective, several large and well-designed clinical trials and population studies have shown that taking β-carotene supplements does not reduce the risk of myocardial infarction, angina, or coronary artery disease; a review of clinical trials showed that β-carotene was associated with a small increase in overall death as well as death from cardiovascular disease.
Evidence strength: The HDL-cholesterol finding from Dunaliella-derived 9-cis β-carotene in fibrate-treated patients is a single, small clinical study and requires independent replication. The broader literature on synthetic all-trans β-carotene supplementation and cardiovascular outcomes is not favorable. Caution is warranted in extrapolating these results.
A randomized, double-blind, placebo-controlled clinical trial titled "9-cis-rich β-carotene powder of the alga Dunaliella reduces the severity of chronic plaque psoriasis" was published in Nutrients in June 2020 (Harari et al., Nutrients. 2020;12(6):1625).
In several experiments, it was demonstrated that a 9-cis β-carotene-enriched diet provided as Dunaliella bardawil powder has a beneficial effect on atherosclerosis, fatty liver, and diabetes mellitus in animal models, as well as on the lipid profile, retinitis pigmentosa, and psoriasis in human trials.
Evidence strength: A single randomized controlled trial provides initial evidence for a therapeutic effect of Dunaliella-derived 9-cis β-carotene in chronic plaque psoriasis. The study requires independent replication in larger populations before conclusions can be drawn.
Clinical evidence highlights β-carotene's efficacy as a systemic photoprotective agent. Research has shown that β-carotene can improve facial wrinkles and elasticity, reduce erythema, increase mRNA levels of collagen I, inhibit the expression of MMP-9, and reduce UV-induced DNA damage. In patients with erythropoietic protoporphyria (EPP) and polymorphic light eruption (PMLE), prolonged supplementation of more than 10 weeks with β-carotene at doses exceeding 12 mg/day significantly reduces UV-induced erythema and photo-dermatosis severity.
Numerous studies have demonstrated that carotenoids, particularly β-carotene, have photoprotective effects — not only through direct light-absorbing properties, but also through antioxidant effects (scavenging reactive oxygen species), regulation of UV light-induced gene expression, modulation of stress-dependent signaling, and/or suppression of cellular and tissue responses like inflammation.
A preclinical study specifically investigated the protective effects of D. salina on UVB radiation-induced corneal oxidative damage in male mice, in which corneal oxidative damage was induced by exposure to UVB radiation at 560 μW/cm² and animals were orally administered D. salina at doses of 0, 123, and 615 mg/kg body weight/day for eight days.
Evidence strength: Systematic photoprotection evidence is derived primarily from studies using β-carotene generically or as mixed carotenoid preparations; robust human trials specifically testing Dunaliella salina biomass as a photoprotective supplement are limited. The photoprotection evidence base is indirect but scientifically plausible given the well-characterized antioxidant mechanisms of its primary constituents.
The green alga Dunaliella salina was investigated for hepatoprotective and antioxidant activity against paracetamol-induced liver damage in rats; male albino Wistar rats overdosed with paracetamol showed liver damage and oxidative stress as indicated by significantly increased serum levels of aminotransferases, alkaline phosphatase, total and direct bilirubin, malondialdehyde, cholesterol, and nitric oxide. Treatment with D. salina methanol extract at doses of 500 and 1000 mg/kg body weight, or the reference hepatoprotective drug silymarin, could significantly (p < 0.05) decrease the liver damage markers.
D. salina decreased hepatic lipid contents, redox status biomarkers, inflammatory cytokines, and showed antiapoptotic properties in a rat model of age-related hepatic steatosis; molecular docking of β-carotene and zeaxanthin on receptors involved in the pathophysiological cascade of steatosis highlighted possible mechanisms underlying the observed therapeutic effect.
Evidence strength: All hepatoprotective evidence is currently from rodent models. No peer-reviewed human clinical trials on hepatoprotection specifically using D. salina preparations have been identified in the published literature. This area remains preclinical.
The extracted β-carotene from Dunaliella salina was assessed for anticancer properties in the human prostate cancer cell line PC-3, showing effective apoptosis of 32% compared to 27% for synthetic β-carotene in flow cytometry analysis.
From a broader supplementation perspective, available evidence does not support the use of β-carotene supplements for preventing cancer; in fact, high β-carotene intake has been linked to higher risk of lung cancer in male smokers and aggressive prostate cancer.
Evidence strength: In vitro anticancer activity is preliminary (cell-line only) and cannot be extrapolated to clinical benefit in humans. The broader β-carotene supplementation literature does not support cancer prevention, and the specific isomeric formulation of Dunaliella-derived carotenoids in cancer contexts has not been adequately studied in human trials.
Multiple animal model experiments demonstrated that a 9-cis β-carotene-enriched diet provided as Dunaliella bardawil powder has a beneficial effect on atherosclerosis, fatty liver, and diabetes mellitus. Research groups have shown that a 9-cis β-carotene-enriched diet, provided as Dunaliella powder, has a beneficial effect on atherosclerosis and diabetes mellitus in animal models and on lipid profiles in human trials.
Evidence strength: Atherosclerosis effects in animal models are promising, and a small human study in fibrate-treated patients showed HDL elevation; however, the human evidence base remains very limited and requires replication.
Dosages reported in the scientific literature vary widely by application and preparation type:
No formally established Recommended Dietary Allowance (RDA), Adequate Intake (AI), or Tolerable Upper Intake Level (UL) specific to Dunaliella salina as a whole-organism supplement has been established by the Institute of Medicine, NIH, or EFSA. The NIH/DRI has set no RDA for β-carotene specifically.
Chronic study in laboratory animals revealed the oral safety of Dunaliella salina; the chronic toxicity was examined by exposing laboratory animals to high doses of Dunaliella salina to estimate the possibility of using it as a safe supplement. Histopathological examination revealed no differences in cardiac, renal, and hepatic architectures between control animals and those fed 100 mg/kg body weight of Dunaliella salina daily for three months.
One published study documented the safety of diets containing 0, 50, and 100 g/kg body weight of Dunaliella bardawil ingested for one year by rats, with no significant differences in blood biochemistry and hematological parameters observed between the algae-supplemented and control animals.
Carotenodermia — a yellowish, harmless discoloration of the skin — can follow excessive intake of foods and supplements containing large amounts of carotenoids. This effect is reversible upon cessation of supplementation and is not associated with toxicity.
The most significant and well-documented safety concern relating to high-dose β-carotene supplementation applies to heavy smokers and individuals with asbestos exposure. Although this literature derives from trials using synthetic all-trans β-carotene rather than Dunaliella-derived preparations specifically, it is directly relevant to any source of supplemental β-carotene in this population.
Two independent trials unexpectedly revealed that heavy smokers (averaging at least 1 package per day for 36 years) receiving long-term β-carotene supplementation at 20 mg/day, or β-carotene at 30 mg/day combined with retinol at 25,000 IU, showed increased rather than decreased incidences of lung cancer.
A meta-analysis of randomized controlled trials demonstrated absence of any protective effect associated with β-carotene supplementation with regard to cancer risk. Epidemiological studies reported no increased lung cancer incidence in heavy smokers at supplemental dose levels of β-carotene varying from 6–15 mg/day for approximately 5 to 7 years. The EFSA Panel concluded that exposure to β-carotene from food additives and food supplements at a level below 15 mg/day does not give rise to concerns about adverse health effects in the general population, including heavy smokers.
These findings support the conclusion that β-carotene supplementation at high doses increases the risk of lung cancer in smokers regardless of the tar or nicotine content of cigarettes smoked, and that all smokers should avoid high-dose β-carotene supplementation.
The production of excessive oxidative β-carotene metabolites via reactions with smoke constituents may be a key event underlying this relationship. Consistent with previous findings, evaluation indicated that consumption of up to 50 mg/day β-carotene does not present safety concerns for the non-smoking general population; heavy smokers consuming less than 15 mg β-carotene/day are not expected to be at an increased risk of lung cancer.
Available evidence does not support the use of β-carotene supplements for preventing cancer; high β-carotene intake has been linked to higher risk of aggressive prostate cancer in some study populations. This signal has emerged predominantly from synthetic all-trans β-carotene studies; whether naturally occurring mixed-isomer preparations from Dunaliella carry the same risk has not been definitively established in clinical trials.
β-Carotene from Dunaliella salina is a fat-soluble compound stored in oily lipid droplets within the alga. Diet affects carotenoid absorption; efficient digestion and absorption of dietary fat, as well as the presence of bile salts, are required for optimal carotenoid uptake. Co-administration with fat-binding agents (such as orlistat or cholestyramine) would be expected to reduce carotenoid absorption, consistent with general lipophilic nutrient pharmacology.
β-Carotene was shown to be stable in oil preparations derived from Dunaliella, with the 9-cis to all-trans β-carotene ratio remaining constant (60:40 g/g) after two years of storage at 4°C. Standardization of preparations to defined isomeric ratios is therefore technically feasible, though product-to-product variation remains a concern in commercial preparations.
Health conditions that Dunaliella salina may help support.
Body systems that Dunaliella salina may help support.
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