Evidence-Based Reviews

Nutraceuticals for traumatic brain injury: Should you recommend their use?

Current Psychiatry. 2017 July;16(7):34-38,40,41-45

References

1. Centers for Disease Control and Prevention. Report to Congress on traumatic brain injury in the United States: epidemiology and rehabilitation. https://www.cdc.gov/traumaticbraininjury/pubs/congress_epi_rehab.html. Updated January 22, 2016. Accessed June 5, 2017.
2. Werner C, Engelhard K. Pathophysiology of traumatic brain injury. Br J Anaesth. 2007;99(1):4-9.
3. Vaishnavi S, Rao V, Fann JR. Neuropsychiatric problems after traumatic brain injury: unraveling the silent epidemic. Psychosomatics. 2009;50(3):198-205.
4. National Institutes of Health Office of Dietary Supplements. Dietary supplement fact sheets. https://ods.od.nih.gov/factsheets/list-all. Accessed June 5, 2017.
5. Institute of Medicine, Food and Nutrition Board. Dietary reference intakes for energy, carbohydrate, fiber, fat, fatty acids, cholesterol, protein, and amino acids. Washington, DC: National Academy of Sciences; 2002.
6. Rao V, Koliatsos V, Ahmed F, et al. Neuropsychiatric disturbances associated with traumatic brain injury: a practical approach to evaluation and management. Semin Neurol. 2015;35(1):64-82.
7. Chew E, Zafonte RD. Pharmacological management of neurobehavioral disorders following traumatic brain injury—a state-of-the-art review. J Rehabil Res Dev. 2009;46(6):851-879.
8. Petraglia AL, Maroon JC, Bailes JE. From the field of play to the field of combat: a review of the pharmacological management of concussion. Neurosurgery. 2012;70(6):1520-1533; discussion 1533.
9. Bengtsson M, Godbolt AK. Effects of acetylcholinesterase inhibitors on cognitive function in patients with chronic traumatic brain injury: a systematic review. J Rehabil Med. 2016;48(1):1-5.
10. Neurobehavioral Guidelines Working Group; Warden DL, Gordon B, McAllister TW, et al. Guidelines for the pharmacologic treatment of neurobehavioral sequelae of traumatic brain injury. J Neurotrauma. 2006;23(10):1468-1501.
11. DeFelice SL. The nutraceutical revolution: its impact on food industry R&D. Trends Food Sci Technol. 1995;6(2):59-61.
12. Cope EC, Morris DR, Levenson CW. Improving treatments and outcomes: an emerging role for zinc in traumatic brain injury. Nutr Rev. 2012;70(7):410-413.
13. Morris DR, Levenson CW. Zinc in traumatic brain injury: from neuroprotection to neurotoxicity. Curr Opin Clin Nutr Metab Care. 2013;16(6):708-711.
14. Young B, Ott L, Kasarskis E, et al. Zinc supplementation is associated with improved neurologic recovery rate and visceral protein levels of patients with severe closed head injury. J Neurotrauma. 1996;13(1):25-34.
15. Fernández-Gajardo R, Matamala JM, Carrasco R, et al. Novel therapeutic strategies for traumatic brain injury: acute antioxidant reinforcement. CNS Drugs. 2014;28(3):229-248.
16. Razmkon A, Sadidi A, Sherafat-Kazemzadeh E, et al. Administration of vitamin C and vitamin E in severe head injury: a randomized double-blind controlled trial. Clin Neurosurg. 2011;58:133-137.
17. Cekic M, Cutler SM, VanLandingham JW, et al. Vitamin D deficiency reduces the benefits of progesterone treatment after brain injury in aged rats. Neurobiol Aging. 2011;32(5):864-874.
18. Aminmansour B, Nikbakht H, Ghorbani A, et al. Comparison of the administration of progesterone versus progesterone and vitamin D in improvement of outcomes in patients with traumatic brain injury: a randomized clinical trial with placebo group. Adv Biomed Res. 2012;1:58.
19. Cernak I, Savic VJ, Kotur J, et al. Characterization of plasma magnesium concentration and oxidative stress following graded traumatic brain injury in humans. J Neurotrauma. 2000;17(1):53-68.
20. Dhandapani SS, Gupta A, Vivekanandhan S, et al. Randomized controlled trial of magnesium sulphate in severe closed traumatic brain injury. The Indian Journal of Neurotrauma. 2008;5(1):27-33.
21. Temkin NR, Anderson GD, Winn HR, et al. Magnesium sulfate for neuroprotection after traumatic brain injury: a randomised controlled trial. Lancet Neurol. 2007;6(1):29-38.
22. Jeter CB, Hergenroeder GW, Ward NH 3rd, et al. Human mild traumatic brain injury decreases circulating branched-chain amino acids and their metabolite levels. J Neurotrauma. 2013;30(8):671-679.
23. Cole JT, Mitala CM, Kundu S, et al. Dietary branched chain amino acids ameliorate injury-induced cognitive impairment. Proc Natl Acad Sci U S A. 2010;107(1):366-371.
24. Aquilani R, Iadarola P, Contardi A, et al. Branched-chain amino acids enhance the cognitive recovery of patients with severe traumatic brain injury. Arch Phys Med Rehabil. 2005;86(9):1729-1735.
25. Aquilani R, Boselli M, Boschi F, et al. Branched-chain amino acids may improve recovery from a vegetative or minimally conscious state in patients with traumatic brain injury: a pilot study. Arch Phys Med Rehabil. 2008;89(9):1642-1647.
26. Kang HJ, Im SH. Probiotics as an immune modulator. J Nutr Sci Vitaminol (Tokyo). 2015;61(suppl):S103-S105.
27. DiPiro JT, Howdieshell TR, Goddard JK, et al. Association of interleukin-4 plasma levels with traumatic injury and clinical course. Arch Surg. 1995;130(11):1159-1162; discussion 1162-1163.
28. Tan M, Zhu JC, Du J, et al. Effects of probiotics on serum levels of Th1/Th2 cytokine and clinical outcomes in severe traumatic brain-injured patients: a prospective randomized pilot study. Crit Care. 2011;15(6):R290.
29. Falcão de Arruda IS, de Aguilar-Nascimento JE. Benefits of early enteral nutrition with glutamine and probiotics in brain injury patients. Clin Sci (Lond). 2004;106(3):287-292.
30. Cuzzocrea S, Mazzon E, Costantino G, et al. Beneficial effects of n-acetylcysteine on ischaemic brain injury. Br J Pharmacol. 2000;130(6):1219-1226.
31. Hoffer ME, Balaban C, Slade MD, et al. Amelioration of acute sequelae of blast induced mild traumatic brain injury by N-acetyl cysteine: a double-blind, placebo controlled study. PLoS One. 2013;8(1):e54163.
32. Eakin K, Baratz-Goldstein R, Pick CG, et al. Efficacy of N-acetyl cysteine in traumatic brain injury. PLoS One. 2014;9(4):e90617.
33. Theadom A, Mahon S, Barker-Collo S, et al. Enzogenol for cognitive functioning in traumatic brain injury: a pilot placebo-controlled RCT. Eur J Neurol. 2013;20(8):1135-1144.
34. Arenth PM, Russell KC, Ricker JH, et al. CDP-choline as a biological supplement during neurorecovery: a focused review. PM R. 2011;3(6 suppl 1):S123-S131.
35. Clark WM. Efficacy of citicoline as an acute stroke treatment. Expert Opin Pharmacother. 2009;10(5):839-846.
36. Guseva MV, Hopkins DM, Scheff SW, et al. Dietary choline supplementation improves behavioral, histological, and neurochemical outcomes in a rat model of traumatic brain injury. J Neurotrauma. 2008;25(8):975-983.
37. Dixon CE, Ma X, Marion DW. Effects of CDP-choline treatment on neurobehavioral deficits after TBI and on hippocampal and neocortical acetylcholine release. J Neurotrauma. 1997;14(3):161-169.
38. Levin HS. Treatment of postconcussional symptoms with CDP-choline. J Neurol Sci. 1991;103(suppl):S39-S42.
39. Zafonte RD, Bagiella E, Ansel BM, et al. Effect of citicoline on functional and cognitive status among patients with traumatic brain injury: Citicoline Brain Injury Treatment Trial (COBRIT). JAMA. 2012;308(19):1993-2000.
40. Perry E, Walker M, Grace J, et al. Acetylcholine in mind: a neurotransmitter correlate of consciousness? Trends Neurosci. 1999;22(6):273-280.
41. Levin HS, Peters BH, Kalisky Z, et al. Effects of oral physostigmine and lecithin on memory and attention in closed head-injured patients. Cent Nerv Syst Trauma. 1986;3(4):333-342.
42. Alvarez XA, Lombardi VR, Corzo L, et al. Oral cerebrolysin enhances brain alpha activity and improves cognitive performance in elderly control subjects. J Neural Transm Suppl. 2000;59:315-328.
43. Ruether E, Husmann R, Kinzler E, et al. A 28-week, double-blind, placebo-controlled study with cerebrolysin in patients with mild to moderate Alzheimer’s disease. Int Clin Psychopharmacol. 2001;16(5):253-263.
44. Wong GK, Zhu XL, Poon WS. Beneficial effect of cerebrolysin on moderate and severe head injury patients: result of a cohort study. Acta Neurochir Suppl. 2005;95:59-60.
45. Chen CC, Wei ST, Tsaia SC, et al. Cerebrolysin enhances cognitive recovery of mild traumatic brain injury patients: double-blind, placebo-controlled, randomized study. Br J Neurosurg. 2013;27(6):803-807.
46. Ziganshina LE, Abakumova T, Vernay L. Cerebrolysin for acute ischaemic stroke. Cochrane Database Syst Rev. 2016;12:CD007026.
47. Barrett EC, McBurney MI, Ciappio ED. ω-3 fatty acid supplementation as a potential therapeutic aid for the recovery from mild traumatic brain injury/concussion. Adv Nutr. 2014;5(3):268-277.
48. Sharma S, Zhuang Y, Ying Z, et al. Dietary curcumin supplementation counteracts reduction in levels of molecules involved in energy homeostasis after brain trauma. Neuroscience. 2009;161(4):1037-1044.
49. Gatson JW, Liu MM, Abdelfattah K, et al. Resveratrol decreases inflammation in the brain of mice with mild traumatic brain injury. J Trauma Acute Care Surg. 2013;74(2):470-475; discussion 474-475.
50. Grey A, Bolland M. Clinical trial evidence and use of fish oil supplements. JAMA Intern Med. 2014;174(3):460-462.
51. Mpandzou G, Aït Ben Haddou E, Regragui W, et al. Vitamin D deficiency and its role in neurological conditions: a review. Rev Neurol (Paris). 2016;172(2):109-122.
52. Karakis I, Pase MP, Beiser A, et al. Association of serum vitamin D with the risk of incident dementia and subclinical indices of brain aging: The Framingham Heart Study. J Alzheimers Dis. 2016;51(2):451-461.
53. Sarris J, Papakostas GI, Vitolo O, et al. S-adenosyl methionine (SAMe) versus escitalopram and placebo in major depression RCT: efficacy and effects of histamine and carnitine as moderators of response. J Affect Disord. 2014;164:76-81.
54. Sarris J, Mischoulon D, Schweitzer I. Omega-3 for bipolar disorder: meta-analyses of use in mania and bipolar depression. J Clin Psychiatry. 2012;73(1):81-86.
55. Sarris J, Stough C, Bousman C, et al. Kava in the treatment of generalized anxiety disorder: a double-blind, randomized, placebo-controlled study. J Clin Psychopharmacol. 2013;33(5):643-648.
56. Hariri M, Azadbakht L. Magnesium, iron, and zinc supplementation for the treatment of attention deficit hyperactivity disorder: a systematic review on the recent literature. Int J Prev Med. 2015;6:83.
57. Gillies D, Sinn JKh, Lad SS, et al. Polyunsaturated fatty acids (PUFA) for attention deficit hyperactivity disorder (ADHD) in children and adolescents. Cochrane Database Syst Rev. 2012;7:CD007986.
58. Ghanizadeh A, Berk M. Zinc for treating of children and adolescents with attention-deficit hyperactivity disorder: a systematic review of randomized controlled clinical trials. Eur J Clin Nutr. 2013;67(1):122-124.
59. U.S. Food and Drug Administration. Can a dietary supplement treat a concussion? No! http://www.fda.gov/forconsumers/consumerupdates/ucm378845.htm. Updated February 13, 2015. Accessed June 5, 2017.
60. Sarris J, Logan AC, Akbaraly TN, et al; International Society for Nutritional Psychiatry Research. Nutritional medicine as mainstream in psychiatry. Lancet Psychiatry. 2015;2(3):271-274.
61. Desai A, Kevala K, Kim HY. Depletion of brain docosahexaenoic acid impairs recovery from traumatic brain injury. PLoS One. 2014;9(1):e86472.
62. Edie CF, Dewan N. Which psychotropics interact with four common supplements. Current Psychiatry. 2005;4(1):16-30.
63. Di Lorenzo C, Ceschi A, Kupferschmidt H, et al. Adverse effects of plant food supplements and botanical preparations: a systematic review with critical evaluation of causality. Br J Clin Pharmacol. 2015;79(4):578-592.
64. National Center for Complementary and Integrative Health. Complementary and alternative medicine: what people aged 50 and older discuss with their health care providers. https://nccih.nih.gov/research/statistics/2010. Published 2011. Accessed June 5, 2017.

Despite their widespread use, the evidence supporting the efficacy of nutraceuticals for patients with TBI is limited. Their effects might vary by population and depend on dose, timing, TBI severity, and whether taken alone or in combination with other nutraceutical or pharmaceutical agents. Fourteen randomized controlled trials (RCTs) have addressed the use of nutraceuticals in TBI (Table 3), but further research is needed to clarify for which conditions they provide maximum benefit.

Nutraceuticals and their potential use in TBI

Zinc is considered essential for optimal CNS functioning. Patients with TBI might be at risk for zinc deficiency, which has been associated with increased cell death and behavioral deficits.^12,13 A randomized, prospective, double-blinded controlled trial examined the effects of supplemental zinc administration (12 mg for 15 days) compared with standard zinc therapy (2.5 mg for 15 days) over 1 month in 68 adults with acute severe closed head injury.¹⁴ The supplemental zinc group showed improved visceral protein levels, lower mortality, and more favorable neurologic recovery based on higher adjusted mean Glasgow Coma Scale score on day 28 and mean motor score on days 15 and 21.

Rodent studies have shown that zinc supplementation could reduce deficits in spatial learning and memory and depression-like behaviors and help decrease stress and anxiety,¹² although no human clinical trials have been conducted. Despite the potential neuroprotective effects of zinc supplementation, evidence exists that endogenous zinc release and accumulation following TBI can trigger cellular changes that result in neuronal death.¹³

Vitamins C and E. Oxidative damage is believed to play a significant role in secondary injury in TBI, so research has focused on the role of antioxidants, such as vitamins C and E, to promote post-TBI recovery.¹⁵ One RCT¹⁶ of 100 adults with acute severe head injury reported that vitamin E administration was associated with reduced mortality and lower Glasgow Outcome Scale (GOS) scores, and vitamin C was associated with stabilized or reduced perilesional edema/infarct on CT scan.

Nutraceuticals for traumatic brain injury: Should you recommend their use?

References

Nutraceuticals and their potential use in TBI

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