White Paper by Madelyn Robinson

Peer Reviewed by Daniel Flynn and Khushboo Verma

Background

Astaxanthin is a natural carotenoid that can be found in certain marine species such as microalgae, fish, crustaceans, and some birds; however, astaxanthin is produced almost exclusively by the green microalgae Haematococcus pluvialis, red yeast, certain mushrooms, and the microbacterium Agrobacterium aurantiacum (Fakhri et al., 2018; Stange, 2016; Sarada et al., 2002). The green microalgae Haematococcus pluvialis is the primary source of astaxanthin, and it produces the carotenoid as a defense mechanism when in unfavorable environments that include a deficiency of nitrogen, high salinity, and high temperature (Ambati et al., 2014; Vidhyavathi et al., 2008). Like many carotenoids, astaxanthin is red-orange in color, and it is responsible for the red or pink coloring of salmon, shrimp, lobsters, crayfish, kril, and other animals that feed on astaxanthin-producing organisms (Galasso et al., 2018; Koomyart et al., 2017). Unlike other carotenoids, astaxanthin is a xanthophyll carotenoid and can not be converted to vitamin A due to its structure (Davinelli et al., 2018; Dufossé, 2009). However, the structure, as seen in Figure 1, allows it to have other more unique properties regarding human health. 

Figure 1:

Astaxanthin’s chemical structure (Fakhri et al., 2018).

Note. Astaxanthin’s unique molecular structure containing polar ends (b) and a nonpolar chain (a) allows it to capture reactive oxygen species, remove high-energy electrons, and preserve the integrity of cell membranes.

Anti-oxidizing Properties

One of the main beneficial aspects of astaxanthin is its anti-oxidizing properties. Aging is associated with the accumulation of oxidative damage to tissues and cells (Junqueira et al., 2004; Bokov et al., 2004). Oxidative stress results when there is an imbalance between oxidants and antioxidants, which causes reactive oxygen species to accumulate. Hence, reducing the reactive oxygen species can counteract the harmful effects of this (Valko et al., 2007). Xanthophyll carotenoids are effective antioxidants due to their ability to grab and remove free radicals, singlet oxygens, and reactive oxygen species by disrupting chain reactions or reacting with them to produce harmless products (Fakhri et al., 2018; Kamath et al., 2008). Astaxanthin specifically is able to scavenge for and capture radicals in both the inner and outer layers of the cell membrane. Early research suggests that it can also help modulate the antioxidant defense system via the Nrf2 pathway, which controls the expression of genes whose proteins detoxify and eliminate reactive oxygen species (Brown et al., 2018; Ngugen et al., 2009). Astaxanthin’s antioxidant activity has been shown to be 100 times greater than other antioxidants including Vitamin E,  alpha-tocopherol, zeaxanthin, lutein, canthaxanthin, and β-carotene (Fakhri et al., 2018; Kobayashi et al., 1997).

Countering Mitochondrial Oxidative Stress

According to the mitochondrial theory of aging, oxidative stress causes mitochondrial damage and increases cellular damage with age (Gershon, 1999). Mitochondrial DNA (mtDNA) is vulnerable to reactive oxygen species. Damaged mtDNA impairs mitochondrial oxidative phosphorylation, which results in an increased production of reactive oxygen species and the decreased production of ATP (Vasileiou et al., 2019; Kim & Kim, 2018). The increased production of reactive oxygen species and overall mitochondrial dysfunction characterize cellular senescence, which causes cell cycle arrest and inflammation (Childs et al., 2015). A study that tested the effects of astaxanthin against mitochondrial oxidative stress found that astaxanthin reduced the mitochondria’s production of oxygen radicals while enhancing the mitochondrial activity; the carotenoid was also found to protect the mitochondria against a decline of membrane function that typically occurs over time (Kidd, 2016). 

Anti-inflammatory Effects

Cellular senescence contributes to the production of pro-inflammatory cytokines that cause chronic inflammation (Freund et al., 2010; Zuo et al., 2019). This age-related chronic inflammation is called inflammaging, and it is associated with an overabundance of reactive oxygen species in the cell; it can lead to oxidation and damage of cellular components, further inflammation, and activation of cell death pathways (Salvioli et al., 2013; Zuo et al., 2019). Since oxidative stress has been shown to be a key contributor to chronic inflammation, astaxanthin’s antioxidant effects also have anti-inflammatory benefits (Zuo et al., 2019). Current research suggests that astaxanthin inhibits the nuclear translocation of NFκB p65 (an activator for molecules that are integral contributors to multiple chronic inflammatory diseases) and prevents the accumulation of reactive oxygen species in NRF2 pathways. (Farruggia et al., 2018). Furthermore, astaxanthin blocks the gene expression of certain downstream inflammatory mediators such as  interleukin-1β, interleukin-6, and tumor necrosis factor-α (Fakhri et al., 2018; Park et al., 2018). 

Figure 2:

Astaxanthin (ASTX) inhibits the expression of pro-inflammatory cytokines (Farruggia et al., 2018).

Further research would be needed to determine exactly how astaxanthin produces all of its anti-inflammatory results, but the aforementioned studies and many additional ones agree that astaxanthin does have these beneficial effects.

Protection Against Neurodegeneration

Aging is the primary risk factor for the majority of neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, and other forms of dementia (Hou et al., 2019; Niccoli & Partridge, 2012). This is largely due to the production and lack of detoxification of reactive oxygen and nitrogen species, and research has proven that increased inflammation, mitochondrial dysfunction, and elevated oxidative stress within the brain all contribute to neurodegeneration (Wang & Michaelis, 2010; Grimmig et al., 2017). As a powerful antioxidant that is able to cross the blood-brain barrier, astaxanthin has been studied to determine its neuroprotective effects, and researchers have largely found that it effectively safeguards neurons from degeneration (Ito et al., 2018, Al-Amin et al., 2015). For example, two studies examined the protective effects of astaxanthin on 6-hydroxydopamine (6-OHDA)-induced apoptosis in the human neuroblastoma cell line SH-SY5Y (Ikeda et al., 2008; Liu et al., 2009). 6-OHDA is neurotoxin that produces reactive oxygen species and leads to a significant decrease in viable dopaminergic SH-SY5Y (Liu et al., 2009). Both studies found that treating SY5Y cells with astaxanthin suppressed 6-OHDA-induced apoptosis in a dose-dependent manner and inhibited 6-OHDA-induced mitochondrial dysfunction. In addition, another study tested the antioxidant and anti-inflammatory effects of astaxanthin on injured PC12 cells, which are classic neuronal cell models that acquire neuronal features when differentiated with nerve growth factor (Chan et al., 2009; Hu et al., 2017). This study concluded that astaxanthin treatments alleviated cell death and DNA fragmentation, increased mitochondrial membrane potential, reduced the formation of reactive oxygen species, and restored Na+/K+ ATPase activity. For these reasons, astaxanthin was concluded to be a potent protective agent against neurodegenerative disorders (Chan et al., 2009).

Reduction in Skin Aging

Astaxanthin’s antioxidant and anti-inflammatory properties also have the ability to reduce skin aging. Skin aging manifests as wrinkles, loss of elasticity, and age spots (liver spots) due to many factors including oxidative stress (Tominaga et al., 2017). UV radiation particularly drives oxidation and the production of reactive oxygen species through a process called photoaging (Rinnerthaler et al., 2015; Galasso et al., 2017).  This can cause skin inflammation characterized by the increased presence of inflammatory cytokines, including those mentioned in Figure 2, that are secreted from UV-irradiated keratinocytes that also produce reactive oxygen species (Fagot et al., 2002;  Ranadive et al., 1989). Thus, suppression of inflammatory cytokines by oxidative stress inhibition is crucial for inhibiting age-related skin deterioration (Johansen, 2020). Multiple studies have concluded that long-term astaxanthin supplementation can inhibit age-related skin deterioration by suppressing the secretion of inflammatory cytokines from UVB-irradiated keratinocytes and matrix metalloproteinases from compromised fibroblasts (Tominaga et al., 2017; Johansen, 2020; Suganuma et al., 2010). 

Natural Sources and Supplements

Astaxanthin-producing algae are often eaten by marine organisms such as salmon, shrimp, lobsters, crayfish, and various birds, so these animals can serve as easy dietary sources of astaxanthin (Galasso et al., 2018). Wild caught salmon and salmonids have the highest amount of astaxanthin out of all other food sources since they contain between 5 and 20 mg of astaxanthin per kg of flesh (1-2% of weight) on average; wild sockeye salmon is arguably the best option to obtain astaxanthin via a food-based approach as it contains around 38 mg of astaxanthin per kg of flesh (2.5% of weight) (Ambati et al., 2014; EFSA, 2005). In comparison, astaxanthin comprises about 0.2% of the dry weight of wild crustaceans including shrimp, crab, and lobster. (Ambati et al., 2014; EFSA 2005).

Conversely, farmed fish and crustaceans tend to have significantly less astaxanthin content than their wild counterparts despite often being supplemented with krill oil or chemically synthesized astaxanthin (EFSA, 2005; Loew, 2012). This is because farmed fish and crustaceans don’t have the same natural access to astaxanthin-producing organisms like they do in the wild. Plus, natural astaxanthin is esterified and has been proven to better prevent oxidation, also making natural and wild sources of astaxanthin the better choice (Nguyen, 2013; Regnier et al., 2015; Capelli et al., 2014). 

Astaxanthin can also be obtained through dietary supplements instead of or in addition to obtaining it from food. The green microalgae H. pluvialis has the highest concentration of astaxanthin (around 3.4-3.8% of dry weight), and many astaxanthin supplements are made from it or from krill oil (Ambati et al., 2014). Supplements can currently be purchased in the form of tablets, capsules, syrups, oils, soft gels, creams, biomass, and granulated powders (Ambati et al., 2014). 

Supplement Dosage

The Food and Drug Administration (FDA) has approved ASX from H. pluvialis for direct human consumption in doses up to 12 mg every day and up to 24 mg per day for no more than 30 days (Davinelli et al., 2018). Recommended dosage depends on a variety of factors including age, health, desired effect, and specific product, but the recommended range is usually between 4 mg and 20 mg per day; however, human clinical studies have safely used astaxanthin in doses that ranges from 4 mg through 100 mg/day (Fassett & Coombes, 2011; Iwamoto et al., 2000). Dosage is flexible since there have been no major side effects or contraindications reported except for an orange tint in the skin or stool after taking large doses for a prolonged period of time (Ash, 2019).

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