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Severe Head Trauma and Omega-3 Fatty Acids

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Diet and Nutrition in Critical Care

Abstract

Severe traumatic brain injury (TBI), with its diverse heterogeneity and prolonged secondary pathogenesis, remains a clinical challenge. Current medical management of TBI patients appropriately focuses on specialized prehospital care, intensive acute clinical care, and long-term rehabilitation but lacks clinically proven effective management with neuroprotective and neuroregenerative agents. Clinical studies thus far have failed to identify an effective treatment strategy as they typically have targeted single enzymatic factors in an attempt to identify a pharmacologic target rather than considering multiple mechanisms of injury with a more holistic approach. A combination of targets controlling aspects of neuroprotection, neuroinflammation, and regeneration is needed. Omega-3 fatty acids (ω-3FA) offer the advantage of this poly-target approach. Although further clinical trial research is needed to establish the true advantage of using ω-3FA, there is a growing body of strong preclinical evidence, and clinical experience suggests that benefits may be possible from aggressively adding substantial amounts of ω-3FA to optimize the nutritional foundation of severe TBI patients. Administration of substantial and optimal doses of ω-3FA early in the course of TBI, even in the prehospital or emergency department setting, has the potential to improve outcomes from this potentially devastating public health problem. With evidence of unsurpassed safety and tolerability, ω-3FA should be considered mainstream, conventional medicine, if conventional medicine can overcome its inherent bias against nutritional, non-pharmacologic therapies.

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Abbreviations

ω-3FAs:

Omega-3 polyunsaturated fatty acids

ω-6FAs:

Omega-6 polyunsaturated fatty acids

AA:

Arachidonic acid

ALA:

Alpha-linolenic acid

APP:

β-Amyloid precursor protein

BDNF:

Brain-derived neurotrophic factor

CaMKII:

Calcium/calmodulin-dependent kinase II

COX:

Cyclooxygenase

CREB:

cAMP-responsive element binding

CT:

Computerized tomography

DAI:

Diffuse axonal injury

DHA:

Docosahexaenoic acid

DHA-Alb:

DHA complexed to albumin

EPA:

Eicosapentaenoic acid

FDA:

Food and Drug Administration (United States)

GCS:

Glasgow Coma Scale

GRAS:

Generally recognizable as safe

H/I:

Hypoxic–ischemic

ICP:

Intracranial pressure

ICU:

Intensive care unit

IL-6:

Interleukin-6

IL-1β:

Interleukin-1 beta

IND:

Investigational new drug

LOX:

Lipoxygenase

LTB4:

Leukotriene B4

Mg:

Milligrams

MRI:

Magnetic resonance imaging

NPD1:

Neuroprotectin D1

PE:

Phosphatidylethanolamine

PEG:

Percutaneous endoscopic gastrostomy

PGE2:

Prostaglandin E2

PLA2:

Phospholipase A2

PS:

Phosphatidylserine

RXR:

Retinoid X receptors

SCI:

Spinal cord injury

SIR-2:

Silent information regulator 2

SOD:

Superoxide dismutase

Syn-1:

Synapsin I

TBI:

Traumatic brain injury

TNF-α:

Tumor necrosis factor alpha

References

  • Armonda R, Bell R, Vo A, et al. Wartime traumatic cerebral vasospasm: recent review of combat casualties. Neurosurgery. 2006;59:1215–25.

    Article  PubMed  Google Scholar 

  • Armstead W. Brain injury impairs prostaglandin cerebrovasodilation. J Neurotrauma. 1998;15:721–9.

    Article  CAS  PubMed  Google Scholar 

  • Armstead W. Superoxide generation links protein kinase C activation to impaired ATP-sensitive K+ channel function after brain injury. Stroke. 1999;30:153–9.

    Article  CAS  PubMed  Google Scholar 

  • Bailes J, Mills J. Docosahexaenoic acid reduces traumatic axonal injury in a rodent head injury model. J Neurotrauma. 2010;27:1617–24.

    Article  PubMed  Google Scholar 

  • Bazan N, Molina M, Gordon W. Docosahexaenoic acid signalolipidomics in nutrition: significance in aging, neuroinflammation, macular degeneration, Alzheimer’s, and other neurodegenerative diseases. Ann Rev Nutr. 2011;31:321–51.

    Article  CAS  Google Scholar 

  • Belayev L, Marcheselli V, Khoutorova L, et al. Docosahexaenoic acid complexed to albumin elicits high-grade ischemic neuroprotection. Stroke. 2005;36:118–23.

    Article  CAS  PubMed  Google Scholar 

  • Berman D, Mozurkewich E, Liu Y, Barks J. Docosahexaenoic acid pretreatment confers neuroprotection in a rat model of perinatal cerebral hypoxia-ischemia. Am J Ob Gyn. 2009;200(305):e1–6.

    Google Scholar 

  • Berman D, Liu Y, Barks J, Mozurkewich E. Treatment with docosahexaenoic acid after hypoxia-ischemia improves forepaw placing in a rat model of perinatal hypoxia-ischemia. Am J Ob Gyn. 2010;203(385):e1–5.

    Google Scholar 

  • Berman D, Mozurkewich E, Liu Y, et al. Docosahexaenoic acid augments hypothermic neuroprotection in a neonatal rat asphyxia model. Neonatology. 2013;104:71–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Blasbalg T, Hibbeln J, Ramsden C, et al. Changes in consumption of omega-3 and omega-6 fatty acids in the United States during the 20th century. Am J Clin Nutr. 2011;93:950–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bradbury J. Docosahexaenoic Acid (DHA): an ancient nutrient for the modern human brain. Nutrients. 2011;3:529–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Calder P. Omega-3 fatty acids and inflammatory processes. Nutrients. 2010;2:355–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chang M, Puder M, Gura K. The use of fish oil lipid emulsion in the treatment of Intestinal Failure Associated Liver Disease (IFALD). Nutrients. 2012;4:1828–50.

    Article  PubMed  PubMed Central  Google Scholar 

  • Chang C, Kuan Y, Li J, et al. Docosahexaenoic acid reduces cellular inflammatory response following permanent focal cerebral ischemia in rats. J Nutr Biochem. 2013;24:2127–37.

    Article  CAS  PubMed  Google Scholar 

  • Coronado V, McGuire L, Sarmiento K, et al. Trends in Traumatic Brain Injury in the U.S. and the public health response: 1995–2009. J Safety Res. 2012;43:299–307.

    Article  PubMed  Google Scholar 

  • Danaei G, Ding E, Mozaffarian D, et al. The preventable causes of death in the United States: comparative risk assessment of dietary, lifestyle, and metabolic risk factors. PLoS Med. 2009;28:e1000058.

    Article  Google Scholar 

  • Diaz-Arrastia R, Kochanek P, Bergold P, et al. Pharmacotherapy of traumatic brain injury: state of the science and the road forward report of the department of defense neurotrauma pharmacology workgroup. J Neurotrauma. 2014;31(2):135–58.

    Article  PubMed  PubMed Central  Google Scholar 

  • Eady T, Khoutorova L, Atkins K, et al. Docosahexaenoic acid complexed to human albumin in experimental stroke: neuroprotective efficacy with a wide therapeutic window. Exp Transl Stroke Med. 2012;4:19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Eady T, Khoutorova L, Anzola D, et al. Acute treatment with docosahexaenoic acid complexed to albumin reduces injury after a permanent focal cerebral ischemia in rats. PLoSOne. 2013;8:e77237.

    Article  CAS  Google Scholar 

  • Eady T, Khoutorova L, Obenaus A, et al. Docosahexaenoic acid complexed to albumin provides neuroprotection after experimental stroke in aged rats. Neurobiol Dis. 2014;62:1–7.

    Article  CAS  PubMed  Google Scholar 

  • EFSA. Scientific opinion on the tolerable upper intake level of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and docosapentaenoic acid (DPA). EFSA J. 2012;10:2815. http://www.efsa.europa.eu/en/efsajournal/pub/2815.htm Accessed 15 December 2013.

  • Farooqui A. n-3 fatty acid-derived lipid mediators in the brain: new weapons against oxidative stress and inflammation. Curr Med Chem. 2012;19:532–43.

    Article  CAS  PubMed  Google Scholar 

  • Farooqui A, Hiser B, Barnes S, Litofsky N. Safety and efficacy of early thromboembolism chemoprophylaxis after intracranial hemorrhage from traumatic brain injury. J Neurosurg. 2013;119:1576–82.

    Article  PubMed  Google Scholar 

  • Faul M, Xu L, Wald M, Coronado V. Traumatic brain injury in the United States: emergency department visits, hospitalizations, and deaths 2002–2006. In: Centers for Disease Control and Prevention; 2010. http://www.cdc.gov/traumaticbraininjury/pdf/blue_book.pdf. Accessed 15 Dec 2013.

  • Figueroa J, Cordero K, Llán M, De Leon M. Dietary omega-3 polyunsaturated fatty acids improve the neurolipidome and restore the DHA status while promoting functional recovery after experimental spinal cord injury. J Neurotrauma. 2013;16:1–16.

    Google Scholar 

  • Goldstein J. No stone unturned: a father’s memoir of his son’s encounter with traumatic brain injury. Dulles: Potomac Books; 2012. p. 242.

    Google Scholar 

  • Gomez-Pinilla F. The influences of diet and exercise on mental health through hormesis. Ageing Res Rev. 2008;7:49–62.

    Article  CAS  PubMed  Google Scholar 

  • Härtl R, Gerber L, Ni Q, Ghajar J. Effect of early nutrition on deaths due to severe traumatic brain injury. J Neurosurg. 2008;109:50–6.

    Article  PubMed  Google Scholar 

  • Hasadsri L, Wang B, Lee J, et al. Omega-3 fatty acids as a putative treatment for traumatic brain injury. J Neurotrauma. 2013;30:897–906.

    Article  PubMed  Google Scholar 

  • Hayden M, Jandial R, Duenas H, et al. Pediatric concussions in sports: a simple and rapid assessment tool for concussive injury in children and adults. Childs Nerv Syst. 2007;23:431–5.

    Article  CAS  PubMed  Google Scholar 

  • Heller A, Rössler S, Litz R, et al. Omega-3 fatty acids improve the diagnosis-related clinical outcome. Crit Care Med. 2006;34:972–9.

    Article  CAS  PubMed  Google Scholar 

  • Hemphill M, Dabiri B, Gabriele S, et al. A possible role for integrin signaling in diffuse axonal injury. PLoSOne. 2011;6:e2289.

    Article  Google Scholar 

  • Katz R. Investigational new drug submission. In: Food and Drug Administration; 2011. http://www.ibrfinc.org/media/fda.pdf. Accessed 15 Dec 2013.

  • Kim H. Biochemical and biological functions of docosahexaenoic acid in the nervous system: modulation by ethanol. Chem Phys Lipids. 2008;153:34–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim H, Spector A. Synaptamide, endocannabinoid-like derivative of docosahexaenoic acid with cannabinoid-independent function. Prostaglandins Leukot Essent Fat Acids. 2013;88:121–5.

    Article  CAS  Google Scholar 

  • Kochanek P, Clark R, Jenkins L. TBI: pathology. In: Zasler N, Katz D, Zafonte R, editors. Brain injury medicine: principles and practice. New York: Demos Medical Publishing; 2007. p. 81–92.

    Google Scholar 

  • Kohli P, Levy B. Resolvins and protectins: mediating solutions to inflammation. Br J Pharmacol. 2009;158:960–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee B, Newberg A. Neuroimaging in traumatic brain imaging. J Am Soc Exp Neurother. 2005;2:372–83.

    Google Scholar 

  • Lewis M, Bailes J. Neuroprotection for the warrior: dietary supplementation with omega-3 fatty acids. Mil Med. 2011;176:1120–7.

    Article  PubMed  Google Scholar 

  • Lewis M, Hibbeln J, Johnson J, et al. Suicide deaths of active-duty US military and omega-3 fatty-acid status: a case-control comparison. J Clin Psych. 2011;72:1585–90.

    Article  CAS  Google Scholar 

  • Lewis M, Ghassemi P, Hibbeln J. Therapeutic use of omega-3 fatty acids in severe head trauma. Am J Emerg Med. 2013;31:5–8.

    Article  Google Scholar 

  • Ling G, Marshall S. Management of traumatic brain injury in the intensive care unit. Neurol Clin. 2008;26:vii.

    Article  Google Scholar 

  • Ling G, Bandak F, Armonda R, et al. Explosive blast neurotrauma. J Neurotrauma. 2009;26:815–25.

    Article  PubMed  Google Scholar 

  • Maas A, Roozenbeek B, Manley G. Clinical trials in traumatic brain injury: past experience and current developments. Neurotherapeutics. 2010;7:115–26.

    Article  PubMed  PubMed Central  Google Scholar 

  • Mayer K, Seeger W. Fish oil in critical illness. Curr Op Clin Nutr Metabolic Care. 2008;11:121–7.

    Article  CAS  Google Scholar 

  • McClave S, Martindale R, Vanek V, et al. Guidelines for the provision and assessment of nutrition support therapy in the adult critically ill patient: Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.). J Parenteral Enteral Nutr. 2009;33:277–316.

    Article  Google Scholar 

  • Meythaler J, Peduzzi J, Eleftheriou E, Novack T. Current concepts: diffuse axonal injury-associated traumatic brain injury. Arch Phys Med Rehab. 2001;82:1461–71.

    Article  CAS  Google Scholar 

  • Michael-Titus A. Omega-3 fatty acids and neurological injury. Prostaglandins Leukot Essent Fat Acids. 2007;77:295–300.

    Article  CAS  Google Scholar 

  • Michael-Titus A, Priestley J. Omega-3 fatty acids and traumatic neurological injury: from neuroprotection to neuroplasticity? Trends Neurosci. 2014;37:30–8.

    Article  CAS  PubMed  Google Scholar 

  • Mills J, Bailes J, Sedney C, et al. Omega-3 fatty acid supplementation and reduction of traumatic axonal injury in a rodent head injury model. J Neurosurg. 2011a;114:77–84.

    Article  CAS  PubMed  Google Scholar 

  • Mills J, Hadley K, Bailes J. Dietary supplementation with the omega-3 fatty acid docosahexaenoic acid in traumatic brain injury. J Neurosurg. 2011b;68:474–81.

    Article  Google Scholar 

  • Moore S, Yoder E, Murphy S, Dutton G, Spector A. Astrocytes, not neurons, produce docosahexaenoic acid (22:6 omega-3) and arachidonic acid (20:4 omega-6). J Neurochem. 1991;56:518–24.

    Article  CAS  PubMed  Google Scholar 

  • Pan H, Kao T, Ou Y, et al. Protective effect of docosahexaenoic acid against brain injury in ischemic rats. J Nutr Biochem. 2009;20:715–25.

    Article  CAS  PubMed  Google Scholar 

  • Park E, Bell J, Baker A. Traumatic brain injury: can the consequences be stopped? Can Med Assoc. 2008;178:1163–70.

    Article  Google Scholar 

  • Pradelli L, Eandi M, Povero M et al. Cost-effectiveness of omega-3 fatty acid supplements in parenteral nutrition therapy in hospitals: a discrete event simulation mode. Clin Nutr. 2014;33(5):785–92.

    Article  CAS  PubMed  Google Scholar 

  • Ramesh G, MacLean A, Philipp M. Cytokines and chemokines at the crossroads of neuroinflammation, neurodegeneration, and neuropathic pain. Mediat Inflamm. 2013:480739. Epub 2013 Aug 12.

    Google Scholar 

  • Rashid M, Katakura M, Kharebava G, et al. N-Docosahexaenoylethanolamine is a potent neurogenic factor for neural stem cell differentiation. J Neurochem. 2013;125:869–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Reilly P. The impact of neurotrauma on society: an international perspective. In: Weber J, Maas A, editors. Neurotrauma: new insights into pathology and treatment. Amsterdam: Elsevier; 2007. p. 5–7.

    Google Scholar 

  • Roberts L, Bailes J, Dedhia H, et al. Surviving a mine explosion. J Am Coll Surg. 2008;207:276–83.

    Article  PubMed  Google Scholar 

  • Rodríguez-Rodríguez A, Egea-Guerrero J, Murillo-Cabezas F, Carrillo-Vico A. Oxidative stress in traumatic brain injury. Curr Med Chem. 2014;21(10):1201–11.

    Article  PubMed  Google Scholar 

  • Rosenberg G. Ischemic brain edema. Prog Cardiovasc Dis. 1999;42:209–16.

    Article  CAS  PubMed  Google Scholar 

  • Russell K, Berman N, Gregg P, Levant B. Fish oil improves motor function, limits blood-brain barrier disruption, and reduces Mmp9 gene expression in a rat model of juvenile traumatic brain injury. Prostaglandins Leukot Essent Fat Acids. 2014;90:5–11.

    Article  CAS  Google Scholar 

  • Saatman K, Duhaime A, Bullock R, et al. Classification of traumatic brain injury for targeted therapies. J Neurotrauma. 2008;25:719–38.

    Article  PubMed  PubMed Central  Google Scholar 

  • Salem N, Litman B, Kim H, Gawrisch K. Mechanisms of action of docosahexaenoic acid in the nervous system. Lipids. 2001;36:945–59.

    Article  CAS  PubMed  Google Scholar 

  • Selassie A, Zaloshnja E, Langlois J, et al. Incidence of long-term disability following traumatic brain injury hospitalization, United States, 2003. J Head Trauma Rehabil. 2008;23:123–31.

    Article  PubMed  Google Scholar 

  • Shin S, Dixon C. Oral fish oil restores striatal dopamine release after traumatic brain injury. Neurosci Lett. 2011;496:168–71.

    Article  CAS  PubMed  Google Scholar 

  • Smith D, Meaney D. Axonal damage in traumatic brain injury. Neuroscientist. 2000;6:483–95.

    Article  Google Scholar 

  • Stein D, Wright D, Kellermann A. Does progesterone have neuroprotective properties? Ann Emerg Med. 2008;51:164–72.

    Article  PubMed  Google Scholar 

  • Streit W, Mrak R, Griffin W. Microglia and neuroinflammation: a pathological perspective. J Neuroinflamm. 2004;1:14.

    Article  Google Scholar 

  • Studer M, Briel M, Leimenstoll B, et al. Effect of different antilipidemic agents and diets on mortality: a systematic review. Arch Intern Med. 2005;165:725–30.

    Article  CAS  PubMed  Google Scholar 

  • Wang T, Van K, Gavitt B, et al. Effect of fish oil supplementation in a rat model of multiple mild traumatic brain injuries. Restor Neurol Neurosci. 2013a;31:647–59.

    PubMed  Google Scholar 

  • Wang X, Dong Y, Han X, et al. Nutritional support for patients sustaining traumatic brain injury: a systematic review and meta-analysis of prospective studies. PLoSOne. 2013b;8:e58838.

    Article  CAS  Google Scholar 

  • Wasserman J, Feldman J, Koenigsberg R. Diffuse axonal injury imaging. Medscape. 2012. http://emedicine.medscape.com/article/339912. Accessed 22 Dec 2013.

  • Weimann A, Braga M, Harsanyi L, et al. ESPEN guidelines on enteral nutrition: surgery including organ transplantation. Clin Nutr. 2006;25:224–44.

    Article  CAS  PubMed  Google Scholar 

  • Williams J, Mayurasakorn K, Vannucci S, et al. N-3 fatty acid rich triglyceride emulsions are neuroprotective after cerebral hypoxic-ischemic injury in neonatal mice. PloSOne. 2013;8:e56233.

    Article  CAS  Google Scholar 

  • Wu A, Ying Z, Gomez-Pinilla F. Omega-3 fatty acids supplementation restores mechanisms that maintain brain homeostasis in traumatic brain injury. J Neurotrauma. 2007;24:1587–95.

    Article  PubMed  Google Scholar 

  • Wu A, Ying Z, Gomez-Pinilla F. The salutary effects of DHA dietary supplementation on cognition, neuroplasticity, and membrane homeostasis after brain trauma. J Neurotrauma. 2011;28:2113–22.

    Article  PubMed  PubMed Central  Google Scholar 

  • Wu A, Ying Z, Gomez-Pinilla F. Exercise facilitates the action of dietary DHA on functional recovery after brain trauma. Neuroscience. 2013;248:655–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xiong Y, Mahmood A, Chopp M. Emerging treatments for traumatic brain injury. Expert Opin Emerg Drugs. 2009;14:67–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yealy D, Hogan D. Imaging after head trauma. Who needs what? Emerg Med Clin North Am. 1991;9:707–17.

    CAS  PubMed  Google Scholar 

  • Zaloshnja E, Miller T, Langlois J, Selassie A. Prevalence of long-term disability from traumatic brain injury in the civilian population of the United States. J Head Trauma Rehabil. 2005;23:394–400.

    Article  Google Scholar 

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Authors and Affiliations

  1. Brain Health Education and Research Institute, 10004 Weatherwood Court, Potomac, MD, 20854, USA

    Michael D. Lewis

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  1. Michael D. Lewis
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Correspondence to Michael D. Lewis .

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Editors and Affiliations

  1. Royal Free London Hospitals, Barnet General Hospital, London, UK

    Rajkumar Rajendram

  2. Division of Diabetes & Nutritional Sciences, Faculty of Life Sciences & Medicine, King’s College London, London, UK

    Rajkumar Rajendram

  3. King Khalid University Hospital, King Saud University Medical City, Riyadh, Saudi Arabia

    Rajkumar Rajendram

  4. Department of Nutrition and Dietetics, Division of Diabetes & Nutritional Sciences, Faculty of Life Sciences & Medicine, King’s College London, London, UK

    Victor R. Preedy

  5. Department of Biomedical Sciences, Faculty of Science & Technology, University of Westminster, London, UK

    Vinood B. Patel

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Lewis, M.D. (2015). Severe Head Trauma and Omega-3 Fatty Acids. In: Rajendram, R., Preedy, V.R., Patel, V.B. (eds) Diet and Nutrition in Critical Care. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-7836-2_114

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