Nutraceuticals for stroke protection: A focus on α-linolenic omega-3 fatty acid
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1
C.N.R.S. Centre National de la Recherche Scientifique, Institut de Pharmacologie Moléculaire et Cellulaire, France
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2
University of Nice, France
Stroke is the third leading cause of death, due to its high incidence and the severity of the insult. Restoration of cerebral blood flow is achieved only in ~5% of patients by recombinant tissue plasminogen activator treatment. Numerous therapeutics identified in preclinical studies aimed at blocking the ischemic cascade failed in clinical trials. This failure in translation from preclinical stroke models to clinical trials has led to a re-evaluation of properties required for therapeutics against stroke to achieve “best-in class” status. Since neuroprotection alone appears ineffective, an emerging direction is to seek drugs which are mechanistically combinatorial in nature, which could protect the whole neurovascular unit and target time-dependent neurotoxic mechanisms.
This capability exists with preconditioning, with research efforts directed to interrogate how the brain protects itself and to discover new molecules that render the brain resistant to subsequent ischemia. Preconditioning elicitBlondeaus complex endogenous neuroprotective responses that act by pleiotropic mechanisms to block death pathways, promote survival pathways and increase resistance. In addition to chemical preconditioners, natural/endogenous compounds - such as the omega-3 polyunsaturated fatty acid, alpha-linolenic acid (ALA) - has been demonstrated to be excellent preconditioners.
Nutraceuticals are a major new concept in preconditioning to combat stroke, in which brain preconditioning is achieved through supplementation of an essential item in the diet. A nutraceutical is the combination of “nutrition” and “pharmaceutical”, as defined in 1989 by Stephen DeFelice to promote the concept of foodstuffs as therapeutics, which demonstrate reasonable clinical evidence of medical benefit, but cannot be claimed as such to the public under present regulatory policy. It is therefore require to narrow the concept of nutraceuticals to a single compound purified from foods that provides protection against disease; such compounds may be sold in medicinal forms not usually associated with food to evaluate nutraceutical efficiency as a drug at the preclinical level, with eventual translation to the clinic or daily life. Consequently, evaluating ALA as an interesting preconditioner against stroke represents a novel view in the context of nutraceutical and functional foods.
The surprising pleiotric properties of ALA to trigger responses that are multi-cellular, mechanistically diverse and with a wide temporal range mirror those responses typically elicited by preconditioning, resulting in neuronal protection, and brain artery vasodilation and neuroplasticity stimulation. In addition, ALA supplementation by modification of the daily diet prevented MCAO-induced mortality and cerebral damage in animal cerebral ischemia models, essentially evading the problem of delivery to the brain, which has normally to be addressed for chemical drugs. Inclusion of omega-3 prophylactically in the diet may induce a preconditioning effect, circumventing what is probably the major barrier in the field, which is timely delivery of a therapeutic (‘time is brain’). Ultimately, the future of preconditioning may largely depend not only upon its successful translation to the clinical arena, but also to daily life. This novel concept of nutraceutical preconditioning may not be restricted to omega-3 PUFAs such as ALA, but may in fact extend to other existing or novel nutraceuticals.
Acknowledgements
This work was supported by ONIDOL, the “Fondation de la Recherche Médicale” and CNRS.
References
For review see:
Blondeau N. Alpha-linolenic omega-3 fatty acid for stroke protection: From brain preconditioning paradigm to nutrition. OCL, Oléagineux, Corps Gras, Lipides 2011;18:271-278.
Blondeau N, Tauskela JS. A new future in brain preconditioning based on nutraceuticals: A focus on a-linolenic omega-3 fatty acid for stroke protection. In: Gidday JM, Perez-Pinzon MA, Zhang JH, eds. Innate tolerance in the cns. New York: Springer New York 2013: pp 133-163.
Nguemeni C, et al. Alpha-linolenic acid: A promising nutraceutical for the prevention of stroke. PharmaNutrition (2013), (under press: http://dx.doi.org/10.1016/j.phanu.2012.12.002)
Keywords:
Stroke,
nutraceutical,
omega-3 polyunsaturated fatty acids,
ischemia/reperfusion injury,
fonctional food,
preconditioning
Conference:
4th Conference of the Mediterrarnean Neuroscience Society, Istanbul, Türkiye, 30 Sep - 3 Oct, 2012.
Presentation Type:
Symposium
Topic:
Abstracts
Citation:
Blondeau
N
(2013). Nutraceuticals for stroke protection: A focus on α-linolenic omega-3 fatty acid.
Conference Abstract:
4th Conference of the Mediterrarnean Neuroscience Society.
doi: 10.3389/conf.fnhum.2013.210.00008
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Received:
28 Jan 2013;
Published Online:
11 Apr 2013.
*
Correspondence:
Dr. Nicolas Blondeau, C.N.R.S. Centre National de la Recherche Scientifique, Institut de Pharmacologie Moléculaire et Cellulaire, Valbonne, 06560, France, blondeau@ipmc.cnrs.fr