Astaxanthin from microalgae, the antioxidant revolution

astaxanthin

Microalgae also unveil their potential, on the ‘nutrition and health’ front, through their ability to produce bioactive substances such as astaxanthin, a carotenoid with extraordinary antioxidant power. Its uses are many, from functional foods and dietary supplements to cosmetics and medicines to aquaculture and animal husbandry.

The microalga Haematococcus pluvialis is the species of greatest economic interest for the production of natural astaxanthin, although other microalgae species (accompanied by yeasts and bacteria) may also come to be used for the extraction of this valuable ingredient (or additive, depending on the uses). (1) An in-depth study.

1) Natural and synthetic astaxanthin

Astaxanthin is a carotenoid known for its reddish color and extraordinary antioxidant properties, far superior to those of other molecules such as vitamins C and E, lutein, and β-carotene. The microalga Haematococcus pluvialis (or H. lacustris) is the first natural source of astaxanthin, the production costs of which, moreover, are not competitive with those of chemical synthesis of the same molecule. Synthetic astaxanthin is therefore widely used in the feed sector (outside of organic supply chains), but its use in foods and food supplements is not authorized in the EU.

The substantial differences (advantages and disadvantages) between natural and synthetic astaxanthin can be identified as follows:

  • natural astaxanthin has markedly higher bioactivity and antioxidant power, higher safety of consumption, lower environmental impact. With the disadvantages of higher production costs, lower yields and lower shelf life,
  • its synthetic replica has antithetical characteristics. And thus low production costs, high availability, greater stability, but also a burdensome environmental impact due to the use of petrochemical reagents and complex, nonrenewable biosynthesis pathways.

2) Astaxanthin from microalgae, the protagonists

The valuable carotenoid can be extracted from some fish species (e.g., krill oil, crustacean exoskeletons) or, in vegan versions, from some microalgae and microorganisms. EFSA, in recognizing Haematococcus pluvialis as having QPS(Qualified Presumption of Safety) status , lists it as the primary source of astaxanthin. With respect to other microalgae-such as Chromochloris zofingiensis and Chlorococcum spp. and Botryococcus braunii-but also with respect to the microorganisms from which it can be derived (see para. 4).

3) Chromochloris zofingiensis, a revolutionary microalga.


Chromochloris zofingiensis
(formerly known as Chlorella zofingiensis) is a green microalga candidate to replace Haematococcus pluvialis(lacustris) specifically for extracting astaxanthin. Indeed, it has a faster ability to multiply and produce biomass, especially under conditions of particular environmental stress.

Extraction and recovery of the carotenoid (i.e., downstream processing) are in turn easier, due to increased cell wall destructive efficiency and metabolite separation. With the only limitation being a lower astaxanthin production yield per cell volume and overall biomass.

Stress conditions induced through high light irradiation, stimulated through blue LEDs (not to be administered in excess to avoid metabolic blockages) and white fluorescent lamps proved optimal at stimulating astaxanthin bioaccumulation in C. zofingiensis (max 39.8 mg/L). To further increase productivity, cell density, nitrogen concentration, as well as the type and intensity of light radiation should also be considered in the future. (2)

4) Alternatives to microalgae

Microorganisms such as yeasts and bacteria can also be used to produce natural astaxanthin. Among them:

  • Phaffia rhodozyma/Xanthophyllomyces dendrorhous. An asexual and sexual form of the same yeast, it was the most widely used source of astaxanthin before the advent of the microalga H. pluvialis. Its productivity is lower but several upcycling trials are underway to produce biomass through the use of low-cost nutrients such as food waste, (3)
  • Paracoccus carotinifaciens. This bacterium does not produce astaxanthin in purity, but rather a mix of carotenoids of which it is the primary component. Through classical mutagenic selection techniques (e.g., UV, chemical treatment), more productive strains were selected, along with more suitable culture parameters.

4) Novel foods based on astaxanthin

The use of astaxanthin in food in the EU is currently permitted in food supplements only, with a warning that it is unsuitable for consumption by children and young people under 14 years of age (see para. 6). The first Novel Food authorization concerns ‘astaxanthin-rich oleoresin from H. pluvialis,’ and a proposal to amend its conditions of use is now under consideration. An additional NF permit application was also submitted for oleoresin and seaweed meal of H. pluvialis. Another novel food with (esters of) astaxanthin, which has already been authorized, is oil from Calanus finmarchicus (small copepod crustacean).

5) Antioxidant action and other health benefits

The benefits of astaxanthin are manifold, due to exponentially higher antioxidant bioactivity than other molecules (Mularczyk et al., 2020). (4) Since it is a fat-soluble compound, its bioavailability increases where taken with oils or fats. Several clinical studies have demonstrated astaxanthin’s ability to reduce inflammation and strengthen the immune system, in addition to its antimicrobial and antiviral activities. Other benefits reported in the literature (Ambati et al., 2014) with varying levels of scientific evidence include:

  • Reduction in blood cholesterol and triglycerides,
  • cardiovascular disease prevention,
  • Reduced DNA damage and lower incidence of cancer,
  • Recovery from mental fatigue,
  • UV skin protection,
  • Maintenance of antioxidant function after oxidative stress from physical activity. (5)

Other clinical studies (Hayashi et al., 2021) have shown astaxanthin’s ability to prevent anxiety, gastric ulcer, and retinal damage, as well as improve cognitive function. Assuming that these effects arise not only fromastaxanthin but also from other AREs(astaxanthin-rich carotenoids) such as adonirubin and adonixanthin. (6)

6) Exposure levels, ADI

EFSA (2020) re-evaluated the safety of astaxanthin on humans, based on exposure from approved novel foods (max 8 mg/day of astaxanthin) and consumption of fish and shellfish containing it due to its use as a feed additive. The results, for target populations, were as follows:

  • adults (70 kg body weight): exposure at 0.174 mg/day per kg body weight is safe, being 13% below the ADI(Acceptable Daily Intake) level set in feed additive opinions at 0.2 mg astaxanthin per kg body weight,
  • Adolescents aged 14 to 17 years (body weight 61.3 kg). The exposure is 0.2 mg/day per kg body weight, equivalent to ADI,
  • Adolescents aged 10 to 13 years (body weight 43.3 kg). The ADI is exceeded for 0.056 mg/day per kg body weight (28% of the total ADI),
  • Children under the age of 10. Exposure ranges between 0.25 and 1 mg/day per kg body weight (ADI exceeded 123-524%).

6) Astaxanthin in aquaculture

Aquaculture is one area where astaxanthin finds extensive use because of its ability to impart the typical ‘salmon’ coloration to farmed fish species, such as salmon trout and the salmon themselves, crustaceans, and even ornamental fish. Nutritional supplementation with astaxanthin then revealed additional benefits for the health production performance of aquaculture animals. It is indeed capable of promoting growth and weight gain.

Administration of astaxanthin together with algal biomass also enables:

  • provide essential amino acids, mono- and polyunsaturated fatty acids, polysaccharides, and vitamins, which enhance the effect of the carotenoid,
  • Promote immune system function, due to antioxidant power, and thus reduce the need for antibiotic use in aquaculture,
  • reduce lipid peroxidation, increasing the stability of the food and its nutritional properties (Lu et al., 2021. See notes 8,9).

7) Astaxanthin in poultry farming

Poultry farming is another area of animal husbandry where astaxanthin is finding great potential both for its antioxidant action and for its positive effects on the immune system and animal health. With a view to reducing and perhaps even eliminating the use of antibiotics and other veterinary drugs, as already pioneered in Italy with Algatan. (10)

Recent studies Experimental on the use of astaxanthin in poultry farming (Zhu et al., 2021; Pertiwi et al., 2022) have indeed demonstrated the usefulness of its intake both in promoting the growth of broiler poultry (broiler), both for the health and welfare of laying hens, with favorable impact on egg quality as well (11,12).

8) Uses in pig farming

Antioxidants not only affect the health and condition of pigs, as well as meat quality. Yang et al. (2006) demonstrated a tenfold reduction in back fat content and an increase in muscle mass after 14 days of feeding 3 mg/kg astaxanthin. (13)

The accumulation of natural astaxanthin in the muscle tissue of pigs, following its inclusion in the feed ration, has an antioxidant action estimated to be four times that of vitamin E. With effects superior to the action of the same molecule added to meat to maintain its quality and preservation.

8) Interim Conclusions.

The domain of microalgae continues to express potentials that are as yet unexpressed or otherwise underestimated. With a view to the production of nutraceutical, medicinal and natural cosmetic ingredients, including through upcycling CO2 and waste from other supply chains, as noted (14,15).

Global algae and microalgae production-as noted in the European Parliament report (2023) following the ‘EU algae initiative’ (2022)-increased from 0.56 to 35.82 million tons, between 1950 and 2019 (16,17,18). And Asia is a major player, with 97 percent.

Research and innovation are essential to develop and validate effective processes and innovative products to stimulate the emergence of the blue bioeconomy in the Old Continent as well. As shown, for example, by the ProFuture research project, in the Horizon program, in Horizon4Proteins (19).

Dario Dongo and Andrea Adelmo Della Penna

Notes

(1) Villaro et al. (2021). Microalgae Derived Astaxanthin: Research and Consumer Trends and Industrial Use as Food. Foods 10:2303, https://doi.org/10.3390/foods10102303

(2) Chen et al. (2017). Enhanced production of astaxanthin by Chromochloris zofingiensis in a microplate-based culture system under high light irradiation. Bioresource Technology 245:518-529, https://doi.org/10.1016/j.biortech.2017.08.102

(3) Gervasi et al. (2019). Astaxanthin production by Xanthophyllomyces dendrorhous growing on a low cost substrate. Agrofor. Syst. 94:1229–1234, https://doi.org/10.1007/s10457-018-00344-6

(4) Mularczyk M, Michalak I, Marycz K. (2020). Astaxanthin and other Nutrients from Haematococcus pluvialis-Multifunctional Applications. Mar Drugs. 2020 Sep 7;18(9):459. doi: 10.3390/md18090459

(5) RR Ambati et al. (2014). Astaxanthin: Sources, Extraction, Stability, Biological Activities and Its Commercial Applications – A Review. Mar. Drugs 12:128-152, https://doi.org/10.3390/md12010128

(6) Hayashi et al. (2021). Commercial Production of Astaxanthin with Paracoccus carotinifaciens. In: Carotenoids: Biosynthetic and Biofunctional Approaches. Advances in Experimental Medicine and Biology 1261:11–20, https://doi.org/10.1007/978-981-15-7360-6_2

(7) EFSA(European Food Safety Authority) NDA Panel (2020). Safety of astaxanthin for its use as a novel food in food supplements. EFSA Journal 18(2):5993, https://doi.org/10.2903/j.efsa.2020.5993

(8) Lu et al. (2021). Astaxanthin as a microalgal metabolite for aquaculture: A review on the synthetic mechanisms, production techniques, and practical application. Algal Research 54:102178. https://doi.org/10.1016/j.algal.2020.102178

(9) For its use in aquaculture, astaxanthin must be authorized as a feed additive (category ‘organoleptic additives’, group ‘colorants’). Three approved additives (astaxanthin, astaxanthin-dimethylsuccinate, and astaxanthin-rich Phaffia rhodozyma biomass) are currently listed in the EU registry, along with their permitted species. And an evaluation is underway on the safety of Paracoccus carotinifaciens, also for use as a feed additive

(10) Dario Dongo, Andrea Adelmo Della Penna. Antibiotic-free poultry farming, the Italian way. GIFT(Great Italian Food Trade). 14.12.20

(11) Yuanzhao Zhu et al. (2021). Astaxanthin supplementation enriches productive performance, physiological and immunological responses in laying hens. Animal Biosci. 2021 Mar; 34(3): 443-448. doi: 10.5713/ab.20.0550

(12) Herinda Pertiwi et al. (2022). Astaxanthin as a Potential Antioxidant to Improve Health and Production Performance of Broiler Chicken Vet. Med. Int. 2022; 2022: 4919442. doi: 10.1155/2022/4919442

(13) Yang, Y.X.; Kim, Y.J.; Jin, Z.; Lohakare, J.D.; Kim, C.H.; Ohh, S.H.; Lee, S.H.; Choi, J.Y.; Chae, B.J. (2006). Effects of dietary supplementation of astaxanthin on production performance, egg quality in layers and meat quality in finishing pigs. AJAS 2006, 19, 1019-1025. doi: 10.5713/ajas.2006.1019

(14) Dario Dongo, Andrea Adelmo Della Penna. Algae and microalgae for food use in Europe, the ABC. GIFT (Great Italian Food Trade). 14.11.22

(15) Dario Dongo, Giulia Pietrollini. Algae and microalgae. Carbon farming and CO2 upcycling. GIFT (Great Italian Food Trade). 18.1.23

(16) European Parliament (2023). The future of the EU algae sector. https://bit.ly/733-114 Research for the PECH Committee doi:10.2861/922543

(17) Marta Strinati. European Commission proposes 23 actions for the seaweed industry. GIFT (Great Italian Food Trade). 23.11.22

(18) European Commission’s Communication ‘Towards a Strong and Sustainable EU Algae Sector (COM/2022/592 final)‘https://eur-lex.europa.eu/legal-content/EN/TXT/?uri=CELEX%3A52022DC0592&qid=1685431066833

(19) Dario Dongo. ProFuture, microalgae to feed the planet. The EU research project. GIFT (Great Italian Food Trade). 18.6.19

+ posts

Dario Dongo, lawyer and journalist, PhD in international food law, founder of WIISE (FARE - GIFT - Food Times) and Égalité.

Graduated in Food Technologies and Biotechnologies, qualified food technologist, he follows the research and development area. With particular regard to European research projects (in Horizon 2020, PRIMA) where the FARE division of WIISE Srl, a benefit company, participates.