Reactive oxygen species (ROS) is a collective term including not only oxygen-centred free radicals, but also some non-radical derivatives of oxygen. ROS, otherwise known as pro-oxidants, are formed as by-products of normal metabolism in our body when food is converted into energy.^[1] Immune cells fighting bacterial infections also release ROS.^[2]

High levels of ROS can initiate harmful alterations in key biomolecules, such as lipids, proteins and DNA in a condition called oxidative stress. Oxidative stress occurs in the body when there is an overproduction of free radicals and ROS on one side, and a deficiency of antioxidants on the other (Figure 1). The efficiency of the body’s own antioxidant defence system reduces with age (Figure 1B), while the overproduction of free radicals/ROS can take place at any point in life, and particularly in response to certain lifestyle and environmental factors (Figure 1C).

Figure 1. Schematic overview with the regulation of oxidative balance. A. Healthy oxidative balance; B. Activity of antioxidant defence reduces as we age, resulting in depletion of antioxidants; C. The overproduction of ROS that takes place in response to endogenous or exogenous factors in any time of life.

In a normal healthy human body, the generation of ROS and other free radicals is kept in check through antioxidant defences. However, when the body is exposed to adverse physicochemical, environmental or pathological stressors, this delicate balance is shifted in favour of pro-oxidants, and results in oxidative stress. Oxidative stress accompanies most, if not all, pathological conditions, including cardiovascular, immunological and neurological disorders,^{[3, 4]}diabetes^[5] and male infertility.^[6] Oxidative stress is also closely linked to premature ageing.^[7]

The antioxidant defence system is a complex network comprising several enzymatic and non-enzymatic antioxidants.^[8] Enzymatic antioxidant defences include superoxide dismutase, glutathione peroxidase, and catalase. There are also several non-enzymatic antioxidants, including vitamins C and E, selenium, and carotenoids such as β-carotene, lycopene, lutein, zeaxanthin and astaxanthin. These function as chain-breaking antioxidants, working in tandem with enzyme antioxidants to temper ROS to within physiological limits. Low intake or impaired availability of dietary antioxidants weakens this important antioxidant network.^[9]

Astaxanthin stands apart from other antioxidants because of its unique chemical properties. While structurally similar to the carotenoid β-carotene, astaxanthin has thirteen conjugated double bonds, whereas β-carotene has eleven. In the cyclohexene structure, it has oxo groups in the fourth and fourth prime positions. The antioxidant activity of carotenoids depends on the length of the electron rich, conjugated, double bond system. An extension of the conjugated double bond system increases the potency of astaxanthin compared to β-carotene and vitamin E.^[10] Additionally, astaxanthin has hydroxyl groups at the third and third prime position, making the molecule somewhat polar.

Nonpolar carotenoids (i.e. β-carotene and lycopene) are located between membrane bilayers and therefore may disrupt the intermolecular packing of the phospholipid molecules.^{[11, 12]} By contrast, polar astaxanthin spans the membrane, with its polar end groups extending toward the head group regions of the membrane bilayer. Astaxanthin position does not modify the structure of constituent membrane lipids.^[11-13] (Figure 2). As a result, astaxanthin acts as a chain-breaking antioxidant by stopping free radical chain reactions and scavenging lipid peroxyl radicals. Furthermore, since astaxanthin spans the cell membrane bilayer, its terminal rings can effectively scavenge ROS on the membrane surface, while its polyene chain is responsible for trapping ROS in the interior of the membrane.^[13]

Figure 2. Astaxanthin orients into optimal hydrophilic and hydrophobic position within cell membrane and acts as a chain-breaking antioxidant. Since astaxanthin spans the cell membrane bilayer, it can effectively scavenge ROS at the membrane surface as well as in the interior of the membrane.

Astaxanthin can use different methods to prevent oxidative stress. Astaxanthin counteracts potentially harmful free radicals by trapping energy (quenching) and the transfer of electrons, or through hydrogen abstraction (scavenging).^{[10, 14-17]} Energy from the high-energy ROS compounds can  be transferred to astaxanthin by direct contact, and that energy is converted to heat ^[10]. In this process of quenching, astaxanthin remains intact so it can undergo further cycles of singlet oxygen quenching. Singlet molecular oxygen is a strong pro-oxidant which displays substantial reactivity towards DNA, proteins, and lipids ^[18].

Comparative studies have shown natural astaxanthin is 6,000 times more powerful than vitamin C, 100 times more powerful than vitamin E, and five times more powerful than β-carotene in its ability to trap energy from singlet oxygen.^[16] (Figure 3) Furthermore, astaxanthin reacts as a strong antioxidant without any pro-oxidative nature.^{[19, 20]} Consequently, astaxanthin is gentle on the body’s cells as it effectively neutralizes harmful ROS.

Figure 3. Natural astaxanthin in comparison to other antioxidants. Natural astaxanthin is more powerful than other antioxidants in trapping energy from singlet oxygen.

1.            Valko M, Leibfritz D, Moncol J, Cronin MTD, et al. (2007) Free radicals and antioxidants in normal physiological functions and human disease. The International Journal of Biochemistry & Cell Biology 39:44-84.

2.            Belikov AV, Schraven B, Simeoni L (2015) T cells and reactive oxygen species. J Biomed Sci 22:85.

3.            Fassett RG, Coombes JS (2009) Astaxanthin, oxidative stress, inflammation and cardiovascular disease. Future Cardiol 5:333-42.

4.            Patel M (2016) Targeting Oxidative Stress in Central Nervous System Disorders. Trends in Pharmacological Sciences 37:768-78.

5.            Maiese K (2015) New Insights for Oxidative Stress and Diabetes Mellitus. Oxidative Medicine and Cellular Longevity 2015:875961.

6.            Ko EY, Sabanegh ES, Jr., Agarwal A (2014) Male infertility testing: reactive oxygen species and antioxidant capacity. Fertility and Sterility 102:1518-27.

7.            Shigenaga MK, Hagen TM, Ames BN (1994) Oxidative damage and mitochondrial decay in aging. Proc Natl Acad Sci U S A 91:10771-8.

8.            Sies H (1993) Strategies of antioxidant defense. Eur J Biochem 215:213-9.

9.            Sies H, Stahl W, Sevanian A (2005) Nutritional, Dietary and Postprandial Oxidative Stress. The Journal of Nutrition 135:969-72.

10.          Miki V (1991) Biological functions and activities of animal carotenoids. Pure & App. Chem. 63:141-43.

11.          McNulty H, Jacob RF, Mason RP (2008) Biologic Activity of Carotenoids Related to Distinct Membrane Physicochemical Interactions. American Journal of Cardiology 101:S20-S29.

12.          McNulty HP, Byun J, Lockwood SF, Jacob RF, et al. (2007) Differential effects of carotenoids on lipid peroxidation due to membrane interactions: X-ray diffraction analysis. Biochim Biochys Acta 1768:

13.          Goto S, Kogure K, Abe K, Kimata Y, et al. (2001) Efficient radical trapping at the surface and inside the phospholipid membrane is responsible for highly potent antiperoxidative activity of the carotenoid astaxanthin. Biochim Biophys Acta 1512:251-8.

14.          Martinez A, Rodriguez-Girones MA, Barbosa A, Costas M (2008) Donator acceptor map for carotenoids, melatonin and vitamins. J Phys.Chem.A 112:9037-42.

15.          Mortensen A, Skibsted LH, Sampson J, Rice-Evans C, et al. (1997) Comparative mechanisms and rates of free radical scavenging by carotenoid antioxidants. FEBS Lett. 418:91-97.

16.          Nishida Y, Yamashita E, Miki W (2007) Quenching Activities of Common Hydrophilic and Lipophilic Antioxidants against Singlet Oxygen Using Chemiluminescence Detection System. Carotenoid Science 11:16-20.

17.          Shimidzu N, Goto M, Miki W (1996) Carotenoids as singlet oxygen quenchers i marine organisms. Fisheries science 62:134-37.

18.          Cadet J, Douki T, Pouget J-P, Ravanat J-L. [14] Singlet oxygen DNA damage products: Formation and measurement. Methods in Enzymology. Vol Volume 319: Academic Press; 2000:143-53.

19.          Martin, Ruck, Schmidt, Sell, et al. (1999) Chemistry of carotenoid oxidation and free radical reactions. Pure Appl. Chem. 71:2253-62.

20.          Beutner S, Bloedorn B, Frixel S, Hernández Blanco I, et al. (2001) Quantitative assessment of antioxidant properties of natural colorants and phytochemicals: carotenoids, flavonoids, phenols and indigoids. The role of β-carotene in antioxidant functions. Journal of the Science of Food and Agriculture 81:559-68.