The shrimp-like microcrustacean Euphausia superba (krill) is one of the most important species among Antarctic marine biota, as it comprises about 50% of the zooplankton biomass (1). Krill consumption by humans has been increasingly suggested to be a potentially healthy nutrition strategy, especially with regard to neuroprotection against progressive cognitive loss (8). With respect to its lipid content, 30% to 65% of the fatty acids in Krill Oil (KO) are incorporated into phospholipids, increasing the bioavailability of the lipid components. Additionally, KO also contains high amounts of the powerful antioxidant astaxanthin ASTA (2,3).
Astaxanthin
In humans, ASTA has been suggested to perform several beneficial functions including inhibition of PUFA oxidation in membranes, and modulation of exacerbated inflammatory responses (4,5). Mitochondria redox metabolism and ROS/RNS-mediated mutations on mtDNA have been commonly observed in various neurological disorders, e.g., AD, PD, as well as in natural aging dysfunction (6). Accordingly, mitochondrial-targeted drugs are now important targets in the field of neurodegenerative diseases (7), and the carotenoid ASTA (isolated or in combination with other compounds) has been strongly suggested to play a role as a putative prophylactic and/or remediation agent against such neuropathies (8-11).
Omega 3 fatty acids
The n-3 PUFAs are known to play a role in nervous system activity, cognitive development, neuroplasticity of nerve membranes, synaptogenesis, and synaptic transmission (12). Imbalances in the n-3/n-6 PUFA ratio may result in increased susceptibility to neuronal damage, as observed in neurodegenerative disease (13). Evidence shows that aging and the associated neurodegenerative processes could be influenced by the consumption of EPA and DHA during the lifetime of humans. Exposure to DHA and EPA enhances adult hippocampal neurogenesis, which is associated with cognitive and behavioural amelioration, enhanced synaptic plasticity, and the formation of new spines (14). Chronic dietary intake of n-3 PUFAs may modulate learning and memory due to the incorporation of these PUFAs into neuronal plasma membranes. With aging, and especially among patients with neurodegenerative diseases, DHA levels in the brain tend to decrease, which suggests that a drop in the n-3/n-6 PUFAs ratio in brain tissues could contribute to deterioration in memory and other cognitive functions (15,16). Moreover, the aging process implies morphological and physiological changes in the brain, resulting in higher ROS/RNS production and a decrease in antioxidant capacity.
Neuroprotection
An observational study, (17) evaluated a cohort of 8085 patients aged 65 years or older with no dementia. After a follow-up period of almost 4 years, they observed that weekly fish consumption presented a correlation with reduced AD risk. AD models indicate a series of beneficial results in response to n-3 PUFA consumption, mainly in terms of synaptic alterations, Aβ accumulation, Tau protein alteration, and cognitive deficits. In a prospective population-based cohort study of people aged ≥55, the association between PUFA intake and the risk of incident PD was evaluated. Intake of total fat, monounsaturated fatty acids (MUFAs), and PUFAs, was significantly associated with a lower risk for PD (18). A double-blinded, placebo-controlled study showed that PD patients taking FO, with or without antidepressants, exhibited reduced depressive symptoms, indicating that n-3 PUFAs had an antidepressant effect or acted as adjuvant therapy with some other medication for PD (19).
Several studies have given rise to the hypothesis that unbalanced n-3 PUFA consumption could affect the physicochemical properties of the neuronal membrane (fluidity, permeability, hydrophobicity, etc.), thereby impacting the speed of signal transduction and the effectiveness of neurotransmission (20-23). Consequently, the neuronal membrane becomes more sensitive to oxidative injury if not properly counterbalanced by antioxidant defences provided by ASTA that sustains the optimal dose-response hormesis ratio (24,25).
References
1 Tarling, G.A. Population dynamics of Northern krill (Meganyctiphanes norvegica Sars). Adv. Mar. Biol. 2010, 57, 59–90.
2 Grynbaum, M.D.; et al. Unambiguous detection of astaxanthin and astaxanthin fatty acid esters in krill (Euphausia superba Dana). J. Sep. Sci. 2005, 28, 1685–1693.
3 Miyashita, K. Function of marine carotenoids. Forum Nutr. 2009, 61, 136–146.
4 Guerin, M.; Huntley, M.E.; Olaizola, M. Haematococcus astaxanthin: Applications for human health and nutrition. Trends Biotechnol. 2003, 21, 210–216.
5 Barros, M.P.; Poppe, S.C.; Souza-Junior, T.P. Putative benefits of microalgal astaxanthin on exercise and human health. Braz. J. Pharmacognos. 2011, 21, 283–289.
6 Dhillon, V.S.; Fenech, M. Mutations that affect mitochondrial functions and their association with neurodegenerative diseases. Mutat. Res. 2014, 759, 1–13.
7 Mao, P.; et al MitoQ, a mitochondria-targeted antioxidant, delays disease progression and alleviates pathogenesis in an experimental autoimmune encephalomyelitis model of multiple sclerosis. Biochim. Biophys. Acta 2013, 1832, 2322–2331.
8 Liu, X.; Osawa, T. Astaxanthin protects neuronal cells against oxidative damage and is a potent candidate for brain food. Forum Nutr. 2009, 61, 129–135.
9 Wang, H.-Q. et al. Astaxanthin upregulates heme oxygenase-1 expression through ERK1/2 pathway and its protective effect against beta-amyloid-induced cytotoxicity. Brain Res. 2010, 1360, 159–167.
10 Lu, Y.-P.; Liu, S.-Y.; Sun, H.; Wu, X.-M.; Li, J.-J.; Zhu, L. Neuroprotective effect of astaxanthin on H2O2-induced neurotoxicity in vitro and on focal cerebral ischemia in vivo. Brain Res. 2010, 1360, 40–48.
11 Chan, K.-C.; et al Antioxidative and anti-inflammatory, neuroprotective effects of astaxanthin and canthaxanthin in nerve growth factor differentiated PC12 cells. J. Food Sci. 2009, 74, H225–H231.
12 Freemantle, E. et al. Omega-3 fatty acids, energy substrates, and brain function during aging. Prostagl. Leukot. Essent. Fatty Acids 2006, 75, 213–220.
13 Yehuda, S.; Rabinovitz, S.; Mostofsky, D.I. Essential fatty acids and the brain: From infancy to aging. Neurobiol. Aging 2005, 26, 98–102.
14 Lukiw, W.J.; Bazan, N.G. Docosahexaenoic acid and the aging brain. J. Nutr. 2008, 138, 2510–2514.
15 Uauy, R.; Dangour, A.D. Nutrition in brain development and aging: Role of essential fatty acids. Nutr. Rev. 2006, 64, S24–S33.
16 Giusto, N.M.; et al. Age-associated changes in central nervous system glycerolipid composition and metabolism. Neurochem. Res. 2002, 27, 1513–1523.
17 Barberger-Gateau, P.; Raffaitin, C.; Letenneur, L.; Berr, C.; Tzourio, C.; Dartigues, J.F.; Alpérovitch, A. Dietary patterns and risk of dementia: The Three-City cohort study. Neurology 2007, 69, 1921–1930.
18 De Lau, L.M.; Schipper, C.M.; Hofman, A.; Koudstaal, P.J.; Breteler, M.M. Prognosis of Parkinson disease: Risk of dementia and mortality: The Rotterdam Study. Arch. Neurol. 2005, 62, 1265–1269.
19 Da Silva, T.M.; et al. Depression in Parkinson’s disease: A double-blind, randomized, placebo-controlled pilot study of omega-3 fatty-acid supplementation. J. Affect. Disord. 2008, 111, 351–359.
20 Mattei, R. et al. Astaxanthin limits fish oil-related oxidative insult in the anterior forebrain of Wistar rats: Putative anxiolytic effects? Pharmacol. Biochem. Behav. 2011, 99, 349–355.
21 Appleton, K.M.; et al. No clear evidence of an association between plasma concentrations of n-3 LCPUFAs and depressed mood in a non-clinical population. Prost Leukot. EFAs 2008, 78, 337–342.
22 Bas, O.; et al. The protective effect of fish n-3 fatty acids on cerebral ischemia in rat hippocampus. Neurochem. Int. 2007, 50, 548–554.
23 King, V.R.;et al. Omega-3 fatty acids improve recovery, whereas omega-6 fatty acids worsen outcome, after spinal cord injury in the adult rat. J. Neurosci. 2006, 26, 4672–4680.
24 Calabrese, V.; et al Cellular stress responses, hormesis paradigm, and vitagenes: Novel targets for therapeutic intervention in neurodegenerative disorders. Antioxid. Redox Signal. 2010, 13, 1763–1811.
25 Jicha, G.A.; Markesbery, W.R. Omega-3 fatty acids: Potential role in the management of early Alzheimer’s disease. Clin. Interv. Aging 2010, 5, 45–61.
