Letter to the Editor: Astaxanthin Reduces the Severity of Intestinal Damage in a Neonatal Rat Model of Necrotizing Enterocolitis

Astaxanthin Reduces the Severity of Intestinal Damage in a Neonatal Rat Model of Necrotizing Enterocolitis

With great interest, we read the first study of the effect of astaxanthin on the rat model of necrotizing enterocolitis (NEC).[1] In the last decade, early recognition and adequate treatment of this disorder has improved clinical outcomes, especially in preterm infants of very low birth weight (<1,500 g). Despite several studies, the pathogenesis of NEC is still the subject of research. In an experimental neonatal rat model of NEC, this study showed that astaxanthin reduces intestinal damage due to its antiapoptotic, antioxidant and anti-inflammatory properties. Astaxanthin was administered orally for 4 days at a dose of 100 mg/kg. There is no doubt that oral administration is probably the most appropriate for this model, but we must not neglect possible other routes of administration such as intraperitoneal or intravenous. The route of administration of the potential drugs is of great importance as some studies have shown limitations after oral administration such as low stability, bioavailability, and bioefficiency with astaxanthin, revealing the need for new biomaterials acting as carriers in vivo.[2] A dose of 100 mg/kg has been used, but we believe that in future studies, the dose may be reduced to keep the dose within the range currently recommended for use in humans, despite the fact that no adverse effects have been found in recent toxicological studies and at much higher doses. Natural astaxanthin is sold in the European Union in a range of products in daily doses up to 12 mg and are approved by national authorities worldwide in daily doses up to 24 mg. Structural features such as size, shape, and polarity are key determinants of astaxanthin ability to fit properly into its molecular environment to increase its own activity.[3] Studies, involving more than 2,000 participants, found no significant toxicity at any dose for natural astaxanthin. Natural astaxanthin has shown an excellent clinical safety profile at short-term daily doses up to 100 mg and long-term daily doses averaging between 8 and 12 mg which is particularly encouraging.[4] The safety of astaxanthin has been assessed in rats after receiving daily oral administration of astaxanthin-rich Haematococcus pluvialis biomass at concentrations up 500 mg/kg/day for 90 days or synthetic astaxanthin in a range between 880 and 1,240 mg/kg/day for 13 weeks.[5] [6] Katsumata et al performed a subchronic toxicity evaluation of a natural astaxanthin-rich carotenoid extract produced from the natural bacteria Paracoccus carotinifaciens suspended in olive oil and administered daily to rats by oral gavage at doses of up to 1,000 mg/kg/day for 13 weeks. The only result highlighted was the excretion of dark-red color feces without reporting any considerable adverse effect.[7] Given these results and current knowledge, it is unlikely that there will be an obstacle to recommending higher than current doses for human use in the future. For optimal administration, the pharmacokinetics and pharmacodynamics of astaxanthin must be investigated in detail. Research on this topic has not been completed.[8] [9] It would also be interesting to see what the results would be if the time of oral administration was reduced or prolonged to determine the most optimal duration of administration. Given the results of previous research, it would certainly be useful to investigate the possible favorable effects of β-carotene, zeaxanthin, canthaxanthin, and violaxanthin, as they are all part of the biosynthetic pathway of astaxanthin.[10]

Publication History

Received: 11 December 2021

Accepted: 07 February 2022

Accepted Manuscript online:
10 February 2022

Article published online:
08 March 2022

• References

• 1 Akduman H, Tayman C, Korkmaz V. et al. Astaxanthin reduces the severity of intestinal damage in a neonatal rat model of necrotizing enterocolitis. Am J Perinatol 2022; 39 (16) 1820-1827
• 2 Zuluaga M, Gueguen V, Letourneur D, Pavon-Djavid G. Astaxanthin-antioxidant impact on excessive reactive oxygen species generation induced by ischemia and reperfusion injury. Chem Biol Interact 2018; 279: 145-158
• 3 Britton G. Structure and properties of carotenoids in relation to function. FASEB J 1995; 9 (15) 1551-1558
• 4 Brendler T, Williamson EM. Astaxanthin: how much is too much? A safety review. Phytother Res 2019; 33 (12) 3090-3111
• 5 Stewart JS, Lignell A, Pettersson A, Elfving E, Soni MG. Safety assessment of astaxanthin-rich microalgae biomass: acute and subchronic toxicity studies in rats. Food Chem Toxicol 2008; 46 (09) 3030-3036
• 6 Vega K, Edwards J, Beilstein P. Subchronic (13-week) toxicity and prenatal developmental toxicity studies of dietary astaxanthin in rats. Regul Toxicol Pharmacol 2015; 73 (03) 819-828
• 7 Katsumata T, Ishibashi T, Kyle D. A sub-chronic toxicity evaluation of a natural astaxanthin-rich carotenoid extract of Paracoccus carotinifaciens in rats. Toxicol Rep 2014; 1: 582-588
• 8 Reboul E. Mechanisms of carotenoid intestinal absorption: where do we stand?. Nutrients 2019; 11 (04) 838
• 9 Parker RS. Absorption, metabolism, and transport of carotenoids. FASEB J 1996; 10 (05) 542-551
• 10 Sathasivam R, Ki JS. A review of the biological activities of microalgal carotenoids and their potential use in healthcare and cosmetic industries. Mar Drugs 2018; 16 (01) 26