The miraculous antioxidant 500 times stronger than vitamin E in a more pragmatic reality has a less romanticized story. However, it is useful in the problem of male infertility and prevention of photodermatitis, “sun allergy”. After a lot of marketing hassle with ridiculous doses of 1-2 mg, we finally got preparations with a little more meaningful doses. An intriguing carotenoid that does not act like provitamin E has found its application in cosmetics “from within”.
When the Dead Sea suddenly changed colour from blue to blood red like in 1980, some saw the phenomenon as a sign from God that dangerous times were approaching. Dangerous times in the Middle East have been a matter of reality for decades.
Scientists were intrigued by this phenomenon and rightly assumed that red was associated with a decrease in salinity during the wet winter of that year. The culprit for this almost biblical phenomenon was the algae Dunaliella. It produces large amounts of carotenoids, including astaxanthin. The end of the world may have already begun, but the late 1980s and early 1990s also marked a new era in the hitherto relatively monotonous use of beta-carotene as the only dietary supplement carotenoid.
Astaxanthin is a natural carotenoid present in various plant kingdoms. It is most often synthesized by algae, but also by the fungi Phaffia rhodozyma and Xanthophyllomyces dendrorhous. Some animals, such as krill, flamingos, and salmon, accumulate astaxanthin through the food chain and incorporate it into their tissue, which thereby becomes intensely pinkish-orange to red in colour. Although astaxanthin is also a dietary supplement, crabs and fish are thought to be the main sources of astaxanthin in the diet. Unlike vitamins, astaxanthin is not a necessary dietary supplement needed for the functioning of the metabolism or hormonal system. Therefore, there is no recommended daily intake. However, like other substances in food, it shows beneficial biological effects.
Discovery of astaxanthin
Although it is often said that astaxanthin was isolated by British scientist Basil Weedon with co-workers, from lobster in 1973, astaxanthin was isolated by German scientists as early as 1938, also from lobster (Kuhn R, Sorensen NA The colouring matters of the lobster (Astacus gammarus L.) Angew Chem 1938; 51:465-466; Über Astaxanthin und Ovoverdin Berichte der deutschen chemischen Gesellschaft (A and B Series) Volume 71, Issue 9, 1879–1888, 7th September 1938). As a talented organic chemist and NMR spectroscopy expert, Basil Weedon discovered its exact structure. At first, astaxanthin was relatively uninteresting. Its main purpose has long been as a food colouring, and as a supplement to animal nutrition to get a better appearance of meat (fish, crabs), or eggs (chickens). Astaxanthin is extremely important for salmon farming where the orange colour of the meat is highly valued. But little by little, interest in the use of astaxanthin as a potentially medicinal substance began to grow, primarily because of its structural similarity to other carotenoids. However, by defining its structure, it was found that astaxanthin is not like beta-carotene, that is, it is not provitamin A.
Effects and mechanisms of action of astaxanthin
The Japanese chemist Wataru Miki is credited with the title “super vitamin E”, i.e. from him the comparison of the antioxidant effect of astaxanthin (and other carotenoids) with vitamin E begins. In his work Biological functions and activities of animal carotenoids from 1991 he compared the antioxidant properties, i.e. the properties of “quenching” (neutralization) of oxygen radicals in in vitro systems. He conducted trials on several systems, including the formation of oxygen radicals in rat mitochondrial supernatants. Until his work, the only more extensive carotenoid was beta-carotene. Wataru Miki was far less surprised by the stronger antioxidant effect of astaxanthin than today’s marketing points out. Namely, in his work he clearly states that in his systems the antioxidant that has more conjugated double bonds is stronger, so it was logical for him that astaxanthin, which has far more such double bonds, is a stronger antioxidant. He determined the following antioxidant effects, expressed as ED50 (concentration where 50% efficiency is achieved):
According to these results, astaxanthin is 4.8 times more powerful antioxidant than β-carotene, and 14.7 times more powerful than α-tocopherol. But how many times is astaxanthin stronger than vitamin E, depends from system to system, that is, it depends on the design of the experiment. Furthermore, in his work, he placed more emphasis on the possibility of using astaxanthin as a food preservative, stronger than vitamin E, and he had very little idea what effects astaxanthin would have on higher organisms.
Still, the star was born. Until the early 1990s, astaxanthin was far from a clinical research. Most of the scientific work from the 1940s to the late 1980s was largely focused on the presence of astaxanthin in various animals and their tissues. Interestingly, even before the discovery of Wataru Miki, Andersen et al. have clearly found that California trout meat spoils more slowly due to the presence of higher amounts of astaxanthin, and have found that astaxanthin protects meat from oxidation processes during storage. However, it was not until 1991 that more serious pharmacological studies of astaxanthin began. Palozza et al. confirm the Japan research, and prove that astaxanthin is more effective in protecting membranes from β-carotene. Astaxanthin itself is a very lipophilic substance- it likes fatty compartments in the body and is incorporated into membranes, just as it does in the organisms in which it is created or accumulated. Here it probably serves as an “extinguisher” of oxygen radicals and actively protects the membrane.
For a long time, scientists lightly thought that carotenoids work because of their provitamin A action, although they were aware that a lot of carotenoids do not make vitamin A, as is the case with astaxanthin. Jyonouchi et al. were the first to notice that the mechanisms of action of β-carotene and astaxanthin differ significantly. Astaxanthin was able to stimulate mouse spleen cells to produce higher levels of class G and M antibodies, in contrast to β-carotene which did not have such an effect. Thus, astaxanthin is at least partially an immunomodulator, although even today it is not its main purpose as a dietary supplement. The authors themselves conclude that astaxanthin acts by a different mechanism of action than vitamin A, but also that it is difficult to understand that the antioxidant effect of astaxanthin is responsible for this effect. This opened up Pandora’s box of questions that the later marketing of astaxanthin, heavily relying on its antioxidant effect, persistently pushed under the rug. This was also the first clearer study of the mechanism of astaxanthin and it should be borne in mind that astaxanthin was then far from being used as a dietary supplement. As evidence of a different mechanism of action, Murillo E. proves that astaxanthin raises HDL cholesterol (good cholesterol), and yet unlike β-carotene.
As a follow-up study of Russian scientists, Tomita et al. in 1993 publish that astaxanthin and β-carotene protect genetically modified mice prone to autoimmune processes from the progression of such processes. And they conclude that this is not related to either vitamin A action or action as an antioxidant.
The big question was, what is the purpose of astaxanthin in the organisms that create it? Fan et al. postulated and proved that in algae Hametococcus pluvialis astaxanthin is not so much an antioxidant, but protects algae from too intense light, which is completely logical. This seemingly only biological issue with no clinical significance came to the fore much later in the application of astaxanthin as photoprotection (protection from solar radiation) from within. A similar conclusion was reached by O’Connor et al. who observed the protective effect of astaxanthin on UV-induced fibroblast stress in an in vitro system. They found that astaxanthin is a hundred times more potent in this system than β-carotene.
Such studies are numerous. Yet what pushed astaxanthin forward was the great “vitamin disappointment” of the 1990s and early 2000s. One after another, vitamins like E and C experienced not only a fiasco in epidemiological studies in protection against tumours and vascular diseases, it has also been found that in some populations taking such antioxidant vitamins even leads to increased risks. The dietary supplement industry began to turn to other molecules, and astaxanthin was one such molecule. Excellent review paper Fasset et al. summarizes these studies which were mainly aimed at protecting the vascular system in experimental models.
Science does not yet have a definitive answer about the mechanism of action of astaxanthin. Several groups have shown that astaxanthin is unlikely to act via retinoid receptors (vitamin A receptors). Recently, Ye et al. found that in the mechanism of action of astaxanthin other types of receptors are involved, transcription factors Sp1 (activated transcription factor 1) and NR1 (NMDA receptor subunit 1), which control many genes. Only the future will show what the exact mechanism of action is, apart from the well-known antioxidant effect.
Clinical studies of astaxanthin
The safety of astaxanthin has been confirmed by several studies, including the one from Spiller et al. from 2003. Comhaire et al. in an already known study examines the effect of 16mg astaxanthin for male infertility and conclude that astaxanthin improves sperm motility parameters through 3 months of use. Several studies such as Karppi et al. have confirmed that astaxanthin reduces lipid oxidation, but with unclear clinical consequences. Yoshida et al. addressed the possible beneficial effects of astaxanthin for HDL cholesterol and triglyceride levels at doses up to 18mg daily and demonstrated the beneficial effect of higher doses of astaxanthin. However, astaxanthin will probably never be a stand-alone therapy for high cholesterol, but only an adjuvant therapy. Tominaga et al. publish as many as two clinical studies of the effects of astaxanthin on skin, measured by the expression of wrinkles and water loss through the skin. They proved that oral supplementation of 6mg of astaxanthin daily improves these parameters, which makes astaxanthin a real “oral cosmetic”.
Indeed, over time, astaxanthin has been shown to be most commonly used in dermatology today, primarily as a prevention of UV-induced skin damage and as a micronutrient for skin beauty. Therefore, it is recommended by some dermatologists today. However, its possible role in protecting the vascular system has not yet been clinically tested (which does not mean that astaxanthin is harmful), and given the negative experiences with vitamins E and C and β-carotene, the results of these tests are expected with uncertainty.
Commercially, most of today’s astaxanthin is derived from the alga Haematococcus pluvialis. Today there is a whole range of preparations that contain astaxanthin, alone or in combination with others. However, some contain a very small dose. It should be borne in mind that a significant number of clinical studies have been designed with doses of 6-16 mg. Therefore, my suggestion is to use doses in that range.