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TBI: Nutritional Treatment and Repair

***This is a brief, general, non-exhaustive recommendation for brain injury nutrition. This should not be considered medical advice. Proper management from a physician should be sought to treat your particular needs, as an individual, before accepting any general recommendations for yours or anyone else's health.***

There are many concomitant pathological complications associated with brain injury, and all must be addressed to properly care for those with post-concussive symptoms. The clinician’s treatment goal for post-concussion syndrome should be:

(A) assist in axonal repair;

(B) reduce inflammation, free radical damage and excitotoxicity;

(C) improve mitochondrial function

(D) restore BBB integrity.(1-3)

This post does not supply information as to why we are treating said listed goals. to understand more please read previous TBI post: HERE

While it may seem that the proper care for a post-concussion syndrome has many components, many of the nutritional protocols overlap in their therapeutic benefit. In order to assist in neurogenesis and synaptogenesis, the treatment goal should target the proliferation of brain derived neurotrophic factor (BDNF) and Nerve Growth Factor (NGF).(6) This can be achieved by the simultaneous administration of DHA (Omega-3), choline and uridine. The combination of these nutrients are the precursor for synaptic formation which can assist in healing the neuronal damage within the brain. Simultaneous ingestion increases brain phosphatides and synaptic protein precursors. This assist in the regeneration of synaptic membranes and proliferation of dendritic spines.(7) Uridine is a difficult supplement to find. The highest natural source of the nutrient is breast milk and organ meats. Other sources are nutritional and brewer's yeast. Choline can be naturally found in eggs, chicken, fish, and legumes.(8) Treatment with fish oil (DHA/EPA) with doses above 10 grams are beneficial for the patients in combination with 10000 IU Vitamin D3. These vitamins can reduce excitotoxicity and the degree of inflammation. Together they promote neuroprotection and increase BDNF.(9, 11) In addition to these supplements the patient must receive adequate levels of B vitamins. Which are crucial in the development of myelin and cell membranes. B Vitamins also assist in the methylation of choline.(12) CDP-Choline (citicoline) has also been shown to decrease apoptosis and oxidative stress. It can also increase the BBB integrity by decreasing Matrix Metallopeptidase (MMP-9).(13) MMP-9 alters the BBB permeability by destroying tight junctions; thus, allowing peripheral immune factors to enter into the brain.(1-2, 13) This combination of supplementation or diet change should be taken a minimum of 2 weeks and can be continued for up to 12 weeks.

Curcumin has been shown to be beneficial in elevating BDNF levels as well as reducing inflammation by inhibiting TNFa and NF-kB.(14-16) The issue with curcumin is the poor bioavailability.(14) Interestingly, studies with the simultaneous intake of melatonin and curcumin have been shown to amplify curcumin’s effect due to melatonin’s lipophilic nature.(15,16).

Together they increase antioxidant upstream regulators DJ-1 and NRF2.(15) The combination of melatonin and curcumin also inhibit MMP-9,which assist in restoring BBB integrity. This is a helpful combination to help those who may be experiencing insomnia. Melatonin can be safely taken daily for up to 20 days. Curcumin can be taken at liberty past the intake of melatonin. The tolerable upper limit of curcumin is approximately 10 grams. The recommended dosages are listed.

Proper mitochondrial function is essential for creating proper energy levels and clearing free radicals.(1-4) It is highly important for patients experiencing post-concussion syndrome to achieve plenty of aerobic exercise as this can increase the signaling to the AMPK pathway and proliferate PGC-1a.(6,17) Resveratrol functions similarly to the mechanism of being in a food deprived state. It increases AMPK pathway to PGC-1a and PPARd which are responsible for mitochondrial biogenesis. Resveratrol also increases SIRT1.(14,18-19) PGC-1a has been shown to increase BDNF levels; both asserting a positive feedback loop. Together both can increase mitochondrial biogenesis and neuroplastic changes.(20) Resveratrol also acts as an anti-inflammatory agent, producing cytokine IL-10, and inhibiting TNFa and NF-kB and COX (which is the main target of NSAIDS). Resveratrol can result in side effects (vomiting, diarrhea, or nausea) with dosages more than 2.5 grams. Thus, it is recommended to take approximate a total of 1000 mg daily (250 mg 4x daily). Resveratrol can safely be taken for long-term treatment, as no issues have been found in any experimental model.(14,18-19)

concussion, resveratrol

A ketogenic diet or time restricted feeding for about a week to two weeks can be essential for the patient. Ketone bodies can easily cross the BBB and can quickly aid in the recovery of axonal damage. A temporary ketogenic diet or caloric restriction assist in upregulating myelin regeneration, fatty acid oxidation, mitochondrial function and biogenesis. While difficult to maintain, it is highly recommended for the patient – such efforts can quickly pay off with a rapid recovery.(20-24)

The length of time to a full recovery will differ on an individual basis and corresponds to the degree of damage which has occurred. The amount of time the patient has taken to seek care post-injury will also determine the time needed to achieve a full recovery; it could also result in a more difficult rehabilitation due to the chronic inflammation and glial scar formation. It is fundamental that the doctor keep a positive rapport with the patient as well as encouraging light aerobic exercise, quiet time for themselves, mind-body exercises such as yoga or meditation and to keep a positive moral.7 While it was not the focus of this article, it is imperative to incorporate other lifestyle interventions, in combination with proper nutrition, to adequately care for the patient.

  1. Diego, L; Gonzales-Portillo, GS; Acosta, S; de la Pena, I; Tajiri, N; Kaneko, Y; Borlongan, CV: Neuroinflammatory responses to traumatic brain injury: etiology, clinical consequences, and therapeutic opportunities. Neuropsychiatric Disease and Treatment.2015;11:97–106

  2. Schimmel, SJ; Acosta, S; Lozano, D: Neuroinflammation in traumatic brain injury: A chronic response to an acute injury. Brain Circ. 2017;3:135-4215.

  3. Talley Watts L. Stimulating mitochondria to protect the brain following traumatic brain injury. Neural Regen Res. 2016;11:1403-416.

  4. Hiebert, JB; Shen, Q; Thimmesch, AR; Pierce JD: Traumatic Brain Injury and Mitochondrial Dysfunction. The American Journal of the Medical Sciences. 2018;350(2):132–138.

  5. Johnson, VE; Weber, MT; Xiao, R; Cullen, DK; Meaney, DF; Stewart, W; Smith, DH: Mechanical disruption of the blood-brain barrier following experimental concussion. Acta Neuropathologica. 2018;135(5):711-726

  6. Almond, A: Postconcussive Syndrome (PCS) Clinical Practice Guideline: Physical Therapy. Ohio State University Wexner Medical Center. Published: August 2017.

  7. Wurtman, RJ: A Nutrient Combination that Can Affect Synapse Formation. Nutrients. 2014;6:1701-1710

  8. Prelicz, CR; Cristian, Lotrean LM: Choline Intake and Its Food Sources in the Diet of Romanian Kindergarten Children. Nutrients. 2017;(9):896.

  9. Richer, AC: Functional Medicine Approach to Traumatic Brain Injury. Medical Acupuncture. 2017;29(4):206-214

  10. Wiedeman, AM; Barr, SI; Green, TJ; Xu, Z; Innis, SM; Kitts, DD: Dietary Choline Intake: Current State of Knowledge Across the Life Cycle. Nutrients. 2018;10(10):1513.

  11. Kumar, PR; Essa, MM; Al-Adawi, S; Dradekh, G; Memon, MA; Akbar, M; Manivasagam, T: Omega-3 Fatty Acids Could Alleviate the Risks of Traumatic Brain Injury – A mini Review: J Tradit Complement Med. 2014;4(2):89–92

  12. Thau-Zuchman, O; Gomes, RN; Dyall, SC; Davies, M; Priestley, JV; Groenendijk, M; De Wilde, MC; Tremoleda, JL; Michael-Titus, AT: Brain Phospholipid Precursors Administered Post-Injury Reduce Tissue Damage and Improve Neurological Outcome in Experimental Traumatic Brain Injury. Journal of Neurotrauma. 2019;26:25-42

  13. Markynov, MY; Gusev, EI: Current knowledge on the neuroprotective and neuroregenerative properties of citicoline in acute ischemic stroke. Journal of Experimental Pharmacology.2015;7:17-28

  14. Velmurugan, BK; Rathinasamy, B; Lohanathan, BP; Thiyagarjan, V; Weng, CF: Neuroprotective Role of Phytochemicals. Molecules. 2018;23,2485

  15. Ismail, IA; El-Bakry, HA; Soliman, SS: Melatonin and tumeric ameliorate aging-induced changes: implication of immunoglobulins, cytokines, DJ-1/NRF2 and apoptosis regulation. Int J Physiol Pathophysiol Pharmacol. 2018;10(2):70-82

  16. Shrestha, S; Zhu, J; Wang, Q; Du, X; Liu, F; et al.: Melatonin potentiates the antitumor effect of curcumin by inhibiting IKKβ/NF-κB/COX-2 signaling pathway. International Journal of Oncology. 2017;51:1249-1260

  17. Chun. CM; Arany, Z; The many roles of PGC-1α in muscle--recent developments. Metabolism. 2014;63(4):441-51.

  18. Ester, Tellone; Galtieri, A; Russo, A; Giardina, B; Ficarra, S: Resveratrol: A Focus on Several Neurodegenerative Diseases. Oxidative Medicine and Cellular Longevity. 2015.

  19. Salehi, B; Mishra, AP; Nigam, M; Sener, B; Kilic, M; et al.: Resveratrol: A Double-Edged Sword in Health Benefits. Biomedicines. 2018;6(91)

  20. Mattson, MP; Moehl, K; Ghena, N; Schmaedick, M; Cheng, A: Intermittent metabolic switching, neuroplasticity and brain health. Nat Rev Neurosci. 2018;19(2):63-80

  21. Maalouf, M; Rho, JM; Mattson, MP: The neuroprotective properties of calorie restriction, the ketogenic diet, and ketone bodies. Brain research reviews. 2009;59:293-315

  22. Mattson, MP; Longo, VD; Harvie, M: Impact of intermittent fasting on health and disease processes. Ageing Research Reviews. 2017;39:46–58

  23. Kalsi, DS: What is the effect of fasting on the lifespan of neurons? Ageing Research Reviews.2015;24:160–165

  24. Paoli, A; Bianco, A; Damiani, E; Bosco, G: Ketogenic Diet in Neuromuscular and Neurodegenerative Diseases. BioMed Research International. 2014.

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