Nutritional Interventions for Traumatic Brain Injury
Traumatic Brain Injury (TBI), also known as a concussion, is a significant cause of death and disability in individuals aged 40 years and younger. Each year, 6.2 million individuals experience a TBI, with our athletes and military personnel at the highest risk (Sharma et al., 2020). The Neurosciences Department at the University of Michigan estimates approximately 3.5 million sports-related concussions occur annually, affecting about 5-10% of athletes in any given season (Concussion in Athletes, n.d.). In 2011, Rigg and Mooney reported that of the 1.6 million American military members deployed to Iraq and Afghanistan, approximately 5-35% had suffered a concussion (Rigg & Mooney, 2011). In addition, TBIs also regularly occur outside of sports and the military. According to the CDC, approximately 224,000 hospital visits in the United States were attributable to TBI in 2017, with 49.1% due to unintentional falls and 24.5% due to motor vehicle accidents (Centers for Disease Control, 2019).
I suffered a significant concussion after falling down the stairs in 2015. My recovery lasted many months and included an overnight hospital stay, three weeks of bed recovery in absolute darkness with minimal interpersonal communication, six weeks without driving a motor vehicle, and multiple months of fatigue, depression, balance issues, and memory loss. Symptoms can be debilitating, and while most concussion sufferers recover within fourteen days, recovery is specific to the individual and can take months or even years. Signs and symptoms include the following:
(Brain Injury Association of America, 2021)
Targeted nutritional support was not a part of my journey until many months post-injury, as it is not the standard of care for TBI in the United States despite scientific research supporting nutritional intervention. Not until I implemented the outlined nutritional interventions did I fully recover. To understand how to support TBI nutritionally, we must first explore what is happening in the body during injury.
Pathophysiological Processes Related to TBI
Multiple pathophysiological processes are initiated in response to a TBI. First, patients develop a hypermetabolic state, increasing energy expenditure and a need for additional nutrition early in the recovery. Stress hormones, such as glucocorticoids, catecholamines, and glucagon, secreted in response to injury, are catabolic and increase metabolic demand. If untreated, hypermetabolism leads to a negative nitrogen balance and loss of skeletal muscle (Kurtz & Rocha, 2020). Glucose typically serves as the brain’s preferred energy source. However, impaired mitochondrial function from injury makes glucose metabolism incredibly inefficient by switching to the anaerobic oxidative pathway, producing only a fraction of the ATP molecules typically produced (Li & Sirko, 2018). In this inefficient energy production process, energy demands are unmet.
In addition, inflammatory cytokines secreted by the immune system affect insulin-signaling pathways, impairing glucose uptake by neurons (Li & Sirko, 2018). If glucose uptake is affected, cells cannot utilize glucose for energy production. However, in response to unmet energy demands, the body provides additional glucose through glycogenolysis and gluconeogenesis, causing hyperglycemia, or elevated blood sugar, to ensue (Kurtz & Rocha, 2020). As a result, the body needs alternative sources of energy other than glucose to support recovery.
An inflammatory cascade also initiates in response to the injury. The brain releases a host of neurotransmitters, chemical messengers in the brain. Excitatory neurotransmitters (i.e., glutamate) result in over-excitation of the nerve cells, increasing energy needs as discussed above, creating cell injury and ultimately cell death (Kurtz & Rocha, 2020; Newton & Dixit, 2012). In addition, free radical formation overwhelms antioxidant systems (Pandya et al., 2014; Sharma et al., 2020). The Blood-Brain Barrier, a protective, tight junction of cells that selectively allow molecules to enter the brain, is broken down, allowing for an influx of immune cells, contributing to inflammation (Dash et al., 2016).
The gut microbiome and the Central Nervous System are linked by a robust communication network called the Gut-Brain Axis. During TBI in animal models, gut dysbiosis and intestinal permeability have been documented within two hours of injury (Rice et al., 2019). Through the Gut-Brain Axis, gut dysfunction negatively influences inflammation, Blood-Brain Barrier permeability, immunity, and mitochondrial dysfunction (Rice et al., 2019).
The impacts of injury are multi-faceted including, a hypermetabolic condition with induced hyperglycemia, similar to Diabetes, a hyperinflammatory state, impaired defenses, and gut dysbiosis. Effective treatment should include nutritional support to target alternative energy pathways, mitochondrial function, inflammation, antioxidant defenses, and gut health.
Nutritional Interventions- Diet
Timing is essential in nutritional support. Nutritional intervention should be initiated within the first 24 hours post-injury, if possible, to preserve skeletal muscle mass and overall function. Provide a minimum of 50% resting energy expenditure (REE), including 1.0 to 1.5 g protein/kg bodyweight for the two weeks after injury (Kurtz & Rocha, 2020).
Ketones are an efficient, alternative fuel source to glucose and can cross the blood-brain barrier. Ketones are produced in the liver from fatty acids when glucose is minimized. The Ketogenic Diet, which encourages ketone production through high-fat consumption, lowers blood glucose levels. In addition, by inducing the mitochondrial uncoupling protein, the Ketogenic Diet reduces the production of free radicals (Yang et al., 2019). Thus, the Ketogenic Diet could help normalize hyperglycemia, meet heightened energy needs in the body, and support antioxidant defenses, making it an excellent fit for TBI patients.
The typical macronutrient ratios in a Ketogenic Diet include daily intake of approximately 70-80% fat, 10-20% protein, and 5-10% carbohydrates (Diet Review: Ketogenic Diet for Weight Loss, 2019). Moderate protein consumption is essential so that additional amino acid intake through protein is not converted to glucose. Dietary supplements of medium-chain fatty acids, such as MCT Oil sourced from coconuts, also increase ketone production. Medium-chain fatty acids differ in metabolism from long-chain fatty acids and are rapidly converted to ketones in the liver. A third way to induce ketone production is through fasting. After 6-8 hours of fasting, ketones appear in the body (Dong et al., 2020). Prolonged periods of fasting are not recommended, however, as increased nutrient intake is vital for TBI recovery and calorie restriction is discouraged.
Nutritional Interventions- Specific Nutrients & Supplements
Omega-3 Polyunsaturated Fatty Acids play a critical role in restoring cellular metabolism and repair (Kurtz & Rocha, 2020). Omega-3s contain pro-resolving mediators, called protectins and resolvins, that modulate innate immunity involved in inflammation (Lust et al., 2020). Two types of Omega-3 fatty acids include EPA and DHA, and both are beneficial in treating TBI. DHA is a component of neuron cell structure, promotes the growth and development of new brain cells, and is involved in the memory and learning centers of the brain. (Lust et al., 2020). EPA is more effective than DHA in improving mood disorders, such as depression (Lust et al., 2020). The recommended dosage is 2-6 grams/day.
Vitamin D has many roles in TBI treatment. Vitamin D can decrease free radical damage, inflammatory cytokine production, and neuronal cell death (Kurtz & Rocha, 2020; Sharma et al., 2020). In addition, when paired with progesterone, Vitamin D can decrease the over-excitation of nerve cells and promote myelin repair, the protective barrier of nerve cells (Sharma et al., 2020). Vitamin D deficiency has been shown to exacerbate the post-TBI symptomology. In one study of 353 patients post-TBI, 80% had low Vitamin D status (Danielson et al., 2018). Dosages remain unclear for TBI treatment. In one published trial, TBI patients were administered 120,000 IU Vitamin D in a single dose in the first 24-hours post-injury with successful outcomes (Sharma et al., 2020). Another study is evaluating 1,000 IU and 100,000 IU single-dose Vitamin D treatments (Arabi et al., 2020).
Magnesium counteracts the excitatory actions of the neurotransmitter glutamate and increases cerebral blood flow, increasing oxygen and improving ATP synthesis (Kurtz & Rocha, 2020). In addition, Magnesium is a cofactor in ATP generation for energy production.
Zinc assists in brain cell growth and development and gene expression related to injury repair (Levenson, 2020). Zinc deficiency also increases oxidative stress, further perpetuating the increase in free radical production caused by TBI. In addition, Zinc is implicated in depression, the most common long-term complication of concussion, and thus sufficient levels are imperative in recovery. A double-blind controlled study of 100 TBI patients had significantly improved outcomes using 120mg of Zinc daily for sixteen days (Levenson, 2020). In another study, 12mg of Zn-sulfate was administered intravenously for 15 days, followed by 22 mg of Zinc Gluconate daily (Kurtz & Rocha, 2020). However, other reports of Zinc toxicity have also been noted to be detrimental to TBI recovery, so a medical provider should monitor supplementation.
Glutathione, a primary intracellular antioxidant, plays a critical role in fighting excessive free radicals. Following injury, both cellular and mitochondrial levels of Glutathione are decreased. Decreased Glutathione is associated with increased tissue damage. Conversely, increasing Glutathione improves mitochondrial function, reduces Blood-Brain Barrier permeability, and decreases brain edema following TBI (Pandya et al., 2014).
Creatine regenerates ATP by donating an additional phosphorous group to ADP, increasing cellular energy (Roschel et al., 2021). Creatine also demonstrates mild antioxidant effects (Lawler et al., 2002). As brain creatine is decreased following TBI, replenishing Creatine could be a valuable strategy in supporting energy needs and enhancing recovery. Evidence is building on the success of Creatine in TBI treatment, but more trials on human subjects are needed. It is also unclear how much Creatine crosses the Blood-Brain Barrier.
Probiotics directly influence bacterial populations in the gut and produce “postbiotics” or bacterial byproducts called Short-Chain Fatty Acids (SCFA), which also target TBI pathophysiology. Treatment with VSL#3, a probiotic supplement of lactobacilli and bifidobacteria species, improved spatial memory in mice with brain injury and reduced inflammation (Rice et al., 2019). The protocol included supplementation for 35 days post-injury.
Nutritional Interventions- Mindfulness
While these recommended interventions help encourage recovery from a TBI, the most impactful resource is space for healing and rest. TBI symptomology is clear evidence the body is injured and needs healing. One study reports a significant reduction in TBI-related mental fatigue using mindfulness-based stress reduction (MBSR) techniques (Johansson et al., 2012). MBSR is a program developed by Kabat-Zinn that includes various mindfulness practices such as breathwork, body scans, meditation, and yoga (Goldin & Gross, 2010). Another study found improved quality of life and perceived self-efficacy using MBSR (Azulay et al., 2013). I found journaling to be incredibly helpful in navigating my journey. Whatever approach is chosen, it is imperative to create space and time to nourish the brain.
Conclusion
Science supports nutritional interventions to effectively and successfully restore homeostasis in the brain post-injury. Unfortunately, nutritionally-based, holistic treatment is not routinely offered to the millions of concussion sufferers each year. Functional providers are well-versed in alternative therapeutic options and understand the biochemistry behind these approaches as well as appropriate dosing. A personalized approach is crafted for each individual to seek the root cause of ailments. If you or a loved one has suffered a concussion, timing is of the essence. Seek treatment immediately and have confidence using nutrition targeted at the mind, body, and spirit as your toolkit.
References:
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