Astaxanthin is a pigment (colored compounds used to color other substances) typically found in water-living organisms. Still, it can be found in other living things, such as algae, salmon, and shrimp. Astaxanthin is a carotenoid (multicolored organic pigments that plants and algae produce).2 More specifically, astaxanthin can be classified as a ketocarotenoid (a ruby-reddish carotenoid).
Brain Health - Oxidative stress might have a huge role in several brain-related health conditions, such as Alzheimer's disease (AD)[1].
In general, oxidative stress is when there aren't enough naturally occurring antioxidants in your body to attack unstable molecules known as free radicals. Free radicals can damage components (parts) within the body, including the hereditary material DNA.
Per a review article, a clinical trial studied astaxanthin in a few healthy older adults. In this clinical trial, older adults in the astaxanthin group had fewer errors in maze tests and experienced quicker reaction times in computer-based memory and thinking tests. These results suggest that astaxanthin may improve brain function.
In another clinical trial discussed in the review article, middle-aged study participants in the astaxanthin group performed better on word memory tests. However, there were no differences in performance between the astaxanthin and placebo groups (people given an intentionally ineffective drug) for participants over 54 years old.
Additionally, from the same review article, other studies showed that astaxanthin improved hand-eye coordination, information processing, and mental or physical fatigue (excessive tiredness).
Even with these encouraging results, it is still challenging to quantify astaxanthin's effects. This is because, in all but one study, astaxanthin was combined with another supplement called sesamin (a fat-reduction supplement from the bark of Fagara plants and sesame oil). This makes it difficult to determine which substance may have been responsible for the positive results.
According to another study in the review article, results suggested that astaxanthin might prevent dementia by lowering phospholipid hydroperoxide (PLOOH) levels in middle-aged and older adults. PLOOH builds up abnormally in the red blood cells (RBCs) of people with AD and dementia.
Astaxanthin Modulates Neuroinflammation by Alleviating Oxidative Stress
Oxidative Stress and Neuroinflammation Neuroinflammation is generally recognized as an intriguingly complex process involving synergistic actions between neurons and different types of glial cells, including microglia, astrocytes, oligodendrocytes, and oligodendrocyte precursor cells. The coordinated interplay of these cells is mediated by neurotransmitters, ions, neurotrophic factors, and cytokines. Microglia are the most acute cells and usually the first to sense abnormalities in the brain microenvironment, even in their presumed resting state (Kreutzberg, 1996; Davalos et al., 2005; Nimmerjahn et al., 2005; Prinz et al., 2019).
Acting as resident macrophages in the brain, microglia primarily play pivotal roles in initiating neuroinflammation. Under stress (e.g., local ischemia, mechanical injury, epilepsy, or exogenous pathogens) (Konat et al., 2006; Lehnardt, 2010; Fitzgerald and Kagan, 2020), injured neurons or oligodendrocytes can release neurotransmitters (i.e., ATP, glutamate, and nitric oxide) to activate microglia.
In an inflammatory model, microglia were recruited to the injury site with the activation of intracellular inflammasomes and the production of pro-inflammatory cytokines (Liu GJ. et al., 2009; Duan et al., 2009; Dibaj et al., 2010; Gundersen et al., 2015; Song et al., 2021). Activated microglia can be broadly categorized into two subtypes, M1 and M2, which have pro- and anti-inflammatory roles, respectively. The traditional M1/M2 terminology for microglia was referenced from a classical macrophage polarization mode, which helped deduce different phenotypes of activated microglia in neuroinflammation processes. However, this biphasic partition appears to be an oversimplification as activated microglia also display mixed phenotypes and intermediate states (Hu et al., 2012; Nakagawa and Chiba, 2015; Orihuela et al., 2016; Ransohoff, 2016).
A dynamic redox equilibrium based on a balance between the production of reactive oxygen/nitrogen species (RONS) and the antioxidant defense system is crucial for maintaining normal cellular processes in the brain. Once excessive RONS overwhelm the defense system comprised of a series of antioxidant molecules and enzymes, oxidative stress occurs, with detrimental effects on various physiological processes.
The brain is particularly susceptible to oxidative stress as elevated RONS can cause oxidative damage to brain resident cells, especially neurons and oligodendrocytes. A vast body of evidence shows that oxidative stress and neuroinflammation are inseparable and closely interrelated. Oxidative stress-induced neuronal damage or apoptosis promotes the release of neurotransmitters, such as ATP and nitrogen monoxide (NO), which trigger the initiation of neuroinflammation (Yang and Zhou, 2019). Moreover, reactive oxygen species (ROS) act as secondary messengers to evoke immune activation, while persistent inflammation can also facilitate oxidative stress (Simpson and Oliver, 2020).
Reactive nitrogen species (RNS) can activate matrix metalloproteinases (MMPs) to trigger blood-brain barrier (BBB) disruption and neuroinflammation (Chen HS. et al., 2018; Hannocks et al., 2019). Consequently, the interplay of RONS generation and neuroinflammation leads to a vicious circle, resulting in persistent damage or degeneration of the brain (Dias et al., 2013; Agrawal and Jha, 2020; Teixeira-Santos et al., 2020; Tewari et al., 2021).
[1] Donoso A, Gonzalez-Duran J, Agurto-Munoz A, et al. Therapeutic uses of natural astaxanthin: an evidence-based review focused on human clinical trials. Pharmacol Res. 2021;166:105479. doi:10.1016/j.phrs.2021.105479
[2] The Putative Role of Astaxanthin in Neuroinflammation Modulation: Mechanisms and Therapeutic Potential https://www.webmd.com/vitamins-and-supplements/astaxanthin
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