The role of nutrition in mild traumatic brain injury rehabilitation for service members and veterans

Abstract

BACKGROUND:

Veterans Affairs and the Department of Defense (DOD) acknowledge that nutrition may be a modifier of mild traumatic brain injury (TBI) sequelae. Military clinicians are considering nutritional supplements and dietary interventions when managing patients with mild TBI. Therefore, clinicians should be familiar with the current evidence for nutritional interventions in mild TBI and special considerations related to the military lifestyle.

OBJECTIVE:

This narrative review aims to summarize the existing evidence surrounding the role of special diets and select nutrients in mild TBI outcomes, gut microbiota changes, and special considerations for Service members and Veterans recovering from mild TBI.

METHODS:

We conducted a literature review in PubMed and Google Scholar limited to nutritional interventions and nine topics with primary focus on mild TBI, although we included some articles related to moderate-to-severe TBI where relevant: 1) ketogenic diet, 2) Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet, 3) omega-3 fatty acids, 4) creatine, 5) vitamin D, 6) weight management, 7) gut microbiota, 8) caffeine, and 9) alcohol. We summarized key findings and safety factors where appropriate for each intervention. We also identified nutritional supplement safety and operational rations considerations and areas in need of further research.

RESULTS:

Preclinical studies and early human trials suggest that the specific nutrients and diets discussed in the current article may offer neuroprotection or benefit during mild TBI rehabilitation. Omega-3 fatty acids, creatine, and vitamin D are generally safe when taken within recommended guidelines.

CONCLUSION:

More evidence is needed to support nutritional recommendations for enhancing neuroprotection and mitigating mild TBI symptoms in humans. The DOD’s Warfighter Nutrition Guide recommends a whole food diet rich in antioxidants, phytonutrients, omega-3 fatty acids, micronutrients, probiotics, and fiber to optimize long-term health and performance.

1. Background

Traumatic brain injury (TBI) is one of the signature injuries of modern warfare. The Department of Defense (DOD) reports nearly 500,000 first-time TBI diagnoses since 2000 (Military Health System and Defense Health Agency, 2024). Mild TBI (mTBI) comprises over 80% of the total TBIs reported, with a subset of these individuals suffering from persistent post-concussive symptoms (PPCS). PPCS negatively impacts overall health, well-being, and occupational performance, compromising our military’s operational readiness. Both the DOD and Veterans Affairs (VA) have several initiatives to optimize brain health with application to mTBI pathophysiology and related sequelae. In their 2011 report, the Committee on Nutrition, Trauma, and the Brain and Institute of Medicine (IOM) emphasized the need for interventional nutrition research to mitigate the effects of TBI on military Service members (SMs). It acknowledges the lack of TBI clinical guidelines for nutritional support and intervention, particularly for mild and moderate TBI. More recently, the VA and DOD identified nutritional status as a potential modifier of mTBI outcomes (The Management and Rehabilitation of Post-Acute Mild Traumatic Brain Injury Work Group, 2021), and emerging evidence supports addressing nutrition, pre- and post-injury, as an essential component of TBI care (Finnegan et al., 2022; Walrand et al., 2021).

Nutrition is one of eight dimensions in the DOD’s Total Force Fitness concept and plays a vital role in optimizing health and performance in the military (Military Health System and Defense Health Agency, 2023). While the initiatives exist, our understanding of nutrition and diet’s role in mitigating the effects of mTBI on SMs’ brain health is nascent. Previous reviews on the role of nutrition in managing TBI have been published, but they have primarily focused on acute and sub-acute phases, typically in critical patients in a hospital setting (Finnegan et al., 2022; Lee & Oh, 2022a). However, this review aims to provide an overview of the evidence related to nutritional interventions for SMs and Veterans who experience persistent symptoms attributed to mTBI, extending beyond the acute and subacute phases, and managed in an outpatient setting. Specifically, we discuss: 1) the impetus for assessing nutrition and diet in SMs with mTBI, 2) the potential role of diet and specific nutrients in TBI pathophysiology and related outcomes, 3) gut microbiome changes and emerging microbiome interventions, and 4) special considerations in the military population when recovering from mTBI.

1.1. Common comorbid conditions and the role of nutrition

Although many factors influence the recovery trajectory of military SMs who sustain mTBI (e.g., psychological factors, resilience, and sleep quality), the injury is associated with several physical and mental health conditions that change over time (Department of Defense, 2021). Common co-occurring mental health conditions (e.g., posttraumatic stress disorder (PTSD), alcohol misuse and dependence, and depression) and physical health conditions (e.g., chronic pain, orthopedic injuries, cardiovascular disease [CVD], and gastrointestinal [GI] disease) are associated with worse outcomes in this population (Department of Defense, 2021). The associations among systemic inflammation, TBI, and commonly co-occurring neuropsychiatric conditions (e.g., depression and PTSD) are well-established (Devoto et al., 2017; Kim et al., 2020; Risbrough et al., 2022). Nutrition has been shown to promote or inhibit systemic inflammation depending on the inflammatory potential of the diet (Shivappa et al., 2013). Further, nutrition affects cognition and mood (Rossa-Roccor et al., 2021; Spencer et al., 2017), with more pro-inflammatory diets associated with more than twice the odds of depression and worse cognitive performance (Bergmans & Malecki, 2017; Frith et al., 2018). Dietary intervention has shown promise in improving major depression symptoms and achieving remission (Jacka et al., 2017). Approaching patients with chronic TBI-related symptoms from a holistic approach, including both a nutritional assessment and targeted nutritional intervention to mitigate long-term sequelae, is an emerging topic in TBI rehabilitative care.

2. Diets of interest

A few of the diets that have garnered interest in TBI and brain health research include the ketogenic, Mediterranean, Dietary Approaches to Stopping Hypertension (DASH), and Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diets. We have discussed the three latter diets in combination as the studies referenced compare these diets.

2.1. Ketogenic diet

Nutritional ketosis can be achieved through endogenous ketone production via dietary manipulation. There are several types of ketogenic diets, including the classic ketogenic diet, the modified ketogenic diet, and the modified Atkins diet. Each of these is characterized by high fat (>70% of calories), low carbohydrate (<5% of calories), and low to moderate consumption of protein (5–10% of calories). Medium chain triglycerides are sometimes used as a fat source to enhance ketone production in the liver. The process of endogenous ketone production through dietary manipulation can take several days to achieve.

The ketogenic diet has shown promise in providing neuroprotective benefits in preclinical TBI trials by altering metabolism and providing an alternative energy source for the brain (Daines, 2021a; Greco et al., 2016a). By reducing glucose availability and promoting the production of ketones, the ketogenic diet may enhance brain energy metabolism, reduce oxidative stress, and support neuronal repair and regeneration (Greco et al., 2016b). Some studies suggest that the ketogenic diet may improve cognitive function and reduce inflammation (Daines, 2021a; Youm et al., 2015). While experimental models suggest potential neuroprotective benefits from a ketogenic diet, further research is needed to fully elucidate the mechanisms and effects of the ketogenic diet in human TBI populations.

Due to the restrictive nature of the diet and the potential for nutrient deficiencies, close monitoring and guidance from a registered dietitian or other qualified health care professional is crucial to ensure adequate nutrition and minimize potential side effects. Ketogenic diets are considered safe but may be contraindicated in patients with certain glucose dysregulation disorders (e.g., type I diabetes), with concomitant use of sodium– glucose cotransporter-2 inhibitors (SGLT2-i), during pregnancy, or while breastfeeding. High risk of myocardial infarction or stroke, undergoing surgery (discontinue for the immediate period before and after), specific cancers (e.g., melanoma, renal cancer) and fat metabolism disorders (e.g., carnitine deficiency, mitochondrial fatty acid β-oxidation disorders) are also contraindications for ketogenic diets (Watanabe et al., 2020). The ketogenic diet should be implemented under medical supervision and tailored to the individual’s specific needs and medical condition.

Exogenous ketone supplementation is also emerging as a means for rapidly achieving ketosis, although transient and not without potential side effects. Exogenous ketones come in ketone precursors (medium chain triglycerides), ketone salts, and ketone esters, all available over-the-counter. Oral ketone supplementation can cause GI distress and use may be limited due to high cost, poor taste, and rapid metabolism, necessitating multiple administrations to maintain elevated blood ketone concentrations (Daines, 2021b). Individuals may monitor ketosis status at home using urinary or blood test strips or devices. Oral ketone supplementation may achieve a blood level concentration range of 0.5 mM to 5.0 mM (Daines, 2021b; Stubbs et al., 2017); however, the level of blood ketone concentration required to achieve beneficial outcomes in TBI is unknown.

2.2. Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet

The relationship between TBI and dementia is still being explored. Emerging evidence suggests that TBI may be a risk factor for dementia, including early-onset dementia, Alzheimer’s disease, and frontotemporal dementia (D. E. Barnes et al., 2014, 2018; Kennedy et al., 2022). The Mediterranean diet is well-known for its association with reduced CVD risk (Dinu et al., 2018) and low inflammatory profile (Hodge et al., 2018). The Dietary Approaches to Stop Hypertension (DASH) diet was developed to reduce CVD risk, emphasizing reducing daily sodium intake to 2,300 mg or less (National Heart, Lung, and Blood Institute, 2021). Researchers from the Rush Memory and Aging Project (MAP) developed a hybrid version of these diets, called the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet, to slow cognitive decline by mitigating CVD risk through diet (Morris, Tangney, Wang, Sacks, Barnes, et al., 2015). These diets are plant-predominant and consist primarily of whole vegetables, fruits, whole grains, nuts, seeds, and legumes, and limit processed foods and red meats. Features of the Mediterranean diet include an emphasis on monounsaturated fats (e.g., olive oil), moderate fish and dairy intake, and low-to-moderate wine consumption (Rishor-Olney & Hinson, 2023). The MIND diet emphasizes high intake of 10 food components associated with a decreased risk of dementia, mainly green leafy vegetables, berries, nuts, fish, and olive oil. It limits five food components high in saturated fats and sugar (e.g., pastries/sweets, fast/fried foods, butter/stick margarine, cheese, and red meat) (Morris, Tangney, Wang, Sacks, Barnes, et al., 2015).

Rush MAP observational studies have demonstrated a decreased risk of Alzheimer’s disease, reduced rate of cognitive decline, lower global Alzheimer’s disease pathology, and less beta-amyloid load in individuals with high adherence to the MIND and Mediterranean diets (Agarwal et al., 2023; Morris, Tangney, Wang, Sacks, Barnes, et al., 2015; Morris, Tangney, Wang, Sacks, Bennett, et al., 2015). Other groups have also found a link between greater MIND diet adherence and reduced incident all-cause dementia (Chen et al., 2023; de Crom et al., 2022). However, a recently published MAP randomized, controlled trial (RCT) did not demonstrate significant changes in cognitive functioning in individuals following the MIND diet intervention over a 3-year follow-up period. Interestingly, both groups showed improved cognitive functioning, although an instructional weight loss intervention in both groups may have confounded these results (L. L. Barnes et al., 2023). More research is still needed to determine the effects of the Mediterranean and MIND diets on long-term brain health outcomes, especially in mTBI.

3. Nutrients of interest

3.1. Omega-3 polyunsaturated fatty acids

Omega-3 fatty acids are long chain, polyunsaturated fatty acids that function in cell membrane structure and fluidity, receptor affinity, and modulation of signal transduction pathways (e.g., inflammation). There are three main types of omega-3 fatty acids: alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). ALA is present primarily in plant-based foods such as walnuts, flaxseed, algae, and chia seeds. In contrast, EPA and DHA are present in animal foods, particularly cold-water fish such as salmon, mackerel, and sardines, and some plant-based foods or supplements such as algae or algae oil. ALA, EPA, and DHA can also be consumed in fortified foods (e.g., juice, eggs) or supplemental form. ALA is poorly converted to the bioactive forms of EPA and DHA; therefore, the optimal intake of EPA and DHA is through animal sources or supplements.

Omega-3 polyunsaturated fatty acids, in dietary and supplement forms, are one of the most well-studied nutrients in TBI literature and may provide therapeutic benefits by mediating inflammatory pathways and targeting mechanisms of secondary injury. Li et al. found in a meta-analysis that higher fish consumption was associated with less depression, a common co-occurring condition with TBI (Li et al., 2016). Providing 2 grams per day of DHA approached significance for association with reduced symptomology and quicker return-to-play time compared to placebo in adolescents with sports-related concussion (Miller et al., 2022). Omega-3 supplementation also attenuated neurofilament-light, a brain injury biomarker, in a dose-response manner in American football players (Heileson et al., 2021; Oliver et al., 2016). While more robust clinical trials are needed to further evaluate the effects of omega-3 s on TBI symptoms and outcomes, up to 40 mg per kilogram of body weight daily or one to three grams per day of combined DHA and EPA are generally safe and are recommended for overall health unless medically contraindicated (e.g., taking warfarin therapy) (National Institutes of Health – Office of Dietary Supplements, 2023).

3.2. Creatine

Creatine provides cellular energy by donating phosphocreatine to the production of adenosine triphosphate (Kreider et al., 2017). While creatine is produced endogenously, small amounts (2–3 grams per day) may be needed through dietary intake, with even greater creatine needs during states of high energy demands, such as metabolic disturbances, which occur during TBI (Kreider et al., 2017). Creatine is primarily found in animal-based foods such as red meat (pork, veal, and beef), seafood (fish and shellfish), and animal milk and may also be consumed in supplemental creatine form. There are several types of creatine supplements (e.g., creatine monohydrate, creatine ethyl ester, creatine hydrochloride), but there are no significant differences in effect between them. Individuals consuming a vegetarian or vegan diet may need 20–30% more creatine than those consuming an omnivorous diet (Kreider & Stout, 2021) and may take synthetic creatine. Creatine supplementation of 3–5 grams daily is generally considered safe for children, adolescents, and adults (Kreider et al., 2017).

Beneficial effects, such as brain and spinal cord neuroprotection and increased functional improvements, have been observed by providing supplemental creatine to rodent models with TBI (Adcock et al., 2002; Sullivan et al., 2000). Early experimental evidence suggests that creatine supplementation may improve brain bioenergetics and inflammation following TBI (Sullivan et al., 2000). Human studies showed creatine supplementation improved memory in vegetarians and cognitive function in children (Benton & Donohoe, 2011; Sakellaris et al., 2006). Research on creatine supplementation to mitigate TBI symptomology is in its infancy, and, while supplementation is generally safe, there are no recommended guidelines for creatine in TBI management.

3.3. Vitamin D

Vitamin D is a class of fat-soluble vitamins, also known as calciferols, that functions more similarly to a hormone than a vitamin. In humans, the two most important calciferols are Vitamin D3 (cholecalciferol) and Vitamin D2 (ergocalciferol). Vitamin D3 is synthesized endogenously within layers of the skin through a reaction with ultraviolet B light while both Vitamin D3 and Vitamin D2 can be ingested exogenously from food and supplements. Vitamin D2 and D3 are both biologically inert and require in vivo metabolism to the active form calcitriol. Natural sources of dietary vitamin D include cold water fish (e.g., salmon, mackerel, sardines), liver, cod liver oil, mushrooms and fortified milk, orange juice, and yogurt (Holick et al., 2011). However, dietary vitamin D intake contributes minimally (i.e., ∼200 IU per day) to serum concentration (Lawrence & Sharma, 2016a). Brief skin exposure (i.e., 10–15 minutes or longer, depending on skin pigmentation) to the sun’s ultraviolet radiation a few times a week may increase circulating 25(OH)D levels longer than oral intake unless medically contraindicated (Haddad et al., 1993; Lawrence & Sharma, 2016b).

Vitamin D promotes calcium absorption in the intestines to maintain bone mineralization and regulate circulating calcium and phosphate levels. Brain neurons and glia also contain vitamin D receptors, leading to research surrounding vitamin D’s role in brain and mental health conditions. Vitamin D reduces inflammation and modulates immune function and glucose metabolism (National Institutes of Health – Office of Dietary Supplements, n.d.).

Vitamin D absorption and optimal concentration levels vary among individuals and there has yet to be an international consensus on vitamin D status categories, with many national guidelines only recognizing severe deficiency (Bleizgys, 2021a). While the National Institutes of Health define Vitamin D levels between 50–125 nmol/L as generally adequate for bone and overall health (National Institutes of Health – Office of Dietary Supplements, n.d.), evidence suggests that levels as high as 100 nmol/L are needed for protection against many diseases, including some cancers and CVD (Bleizgys, 2021b). Optimal serum 25(OH)D levels for TBI benefits in humans remain unknown.

The current literature on vitamin D’s role in TBI is limited, however, emerging research suggests that vitamin D may provide neuroprotective benefits after TBI through several mechanisms, such as reducing inflammation, stimulating neurotrophic factors, and regulating oxidative stress (Lawrence & Sharma, 2016a). Preclinical trials have demonstrated therapeutic value from vitamin D as a monotherapy or in conjunction with progesterone (Aminmansour et al., 2012; Hua et al., 2012). Vitamin D in combination with progesterone elicited a more favorable recovery than placebo or progesterone alone three months after severe TBI (Aminmansour et al., 2012) and enhanced memory in experimental TBI models (Hua et al., 2012). Vitamin D supplementation also improved the level of consciousness at seven days post injury and reduced inflammatory biomarkers in ICU patients admitted with TBI, compared to placebo in a double-blind RCT (Sharma et al., 2020). Approximately 70% of the U.S. population is considered to have deficient or insufficient levels of vitamin D, using Endocrine Society standards, and vitamin D deficiency has been associated with neuronal injury (Lawrence & Sharma, 2016a; X. Liu et al., 2018). Vitamin D supplementation of 1000 to 2000 IU/day is generally safe. Given (1) the high prevalence of vitamin D insufficiency; (2) vitamin D supplementation is inexpensive and effective; and (3) early studies showing a therapeutic benefit for a vitamin D sufficient status and vitamin D supplementation in TBI, further study is warranted into the role of vitamin D in the management of TBI.

4. Nutritional supplement safety

Clinicians should consider the source and quality of over-the-counter dietary supplements when treating patients already taking them or when recommending them to patients. Dietary supplements are not regulated for safety or efficacy. The best approach to ensure the supplement contains the ingredients listed on the label and does not contain harmful contaminants is to look for a seal indicating third-party testing and certification, such as that of the NSF or United States Pharmacopeia (USP). The DOD’s Operation Supplement Safety (OPSS) website is open access and a reliable resource for dietary supplement safety information (Uniformed Services University, Consortium for Health and Military Performance, n.d.) (see Table 1). Some dietary supplements may interact with prescription medications; therefore, clinicians should always assess for the risk of drug-nutrient interactions before recommending any dietary supplements.

Table 1.

Open access online nutrition resources

Resource	Description
Operation Supplement Safety https://www.opss.org/	Evidence-based DOD dietary supplement program for SMs, their families, healthcare providers, and leaders to achieve human performance optimization
Automated Self-Administered 24-hour (ASA-24®) Dietary Assessment Tool https://epi.grants.cancer.gov/asa24/	Free web-based tool; enables self-administered 24-hour diet recalls and/or single or multi-day food records for individuals with immediate results
Human Performance Resources (CHAMP) https://www.hprc-online.org/	DOD clearinghouse for Human Performance Optimization and Total Force Fitness information; includes articles, recipes, and infographics on various lifestyle and performance nutrition topics
Warfighter Nutrition Guide (CHAMP) https://www.hprc-online.org/nutrition/warfighter-nutrition-guide	Contains strategies and recommendations for all aspects of performance nutrition for military SMs; covers the spectrum of nutritional needs to optimize warfighter performance under the most rigorous conditions
Go for Green (G4 G) https://www.hprc-online.org/nutrition/go-green	Joint service, evidence-based, performance nutrition initiative that improves the military food environment; provides resources to implement G4 G in DOD dining facilities and galleys
American Sports and Performance Dietitians Association (ASPDA) https://sportsrd.org/	National not-for-profit organization with a “food first” approach; provides evidence-based exercise and sports nutrition knowledge through educational resources, including free infographics, handouts, and fact sheets
American College of Lifestyle Medicine https://lifestylemedicine.org/	National non-profit medical professional society; advances evidence-based lifestyle medicine to treat, reverse, and prevent non-communicable, chronic disease through free educational webinars, practice resources, and networking

Note. DOD = Department of Defense; SMs = service members; CHAMP = Consortium for Health and Military Performance.

5. Weight management

Individuals who sustain a TBI commonly experience changes in body mass following injury. Weight management in individuals with TBI is particularly challenging due to the unique factors associated with TBI. These factors include physical limitations that may restrict exercise and movement, changes in appetite and eating patterns, cognitive deficits that can impair decision-making related to food choices, and sleep disturbances that can disrupt normal metabolic processes (Crenn et al., 2014; Lee & Oh, 2022b). The presence of comorbidities such as depression and anxiety can further complicate the management of weight in TBI patients (Crenn et al., 2014). Furthermore, TBI patients may be at increased risk of alcohol abuse, which can be another source of excess calories leading to weight gain (Pagulayan et al., 2016).

Individuals may experience physical function limitations, sleep dysregulation, and changes in neurobehavioral patterns following TBI, which may contribute to post-injury weight gain (Dreer et al., 2018). Excess weight can increase the risk of chronic diseases such as CVD and diabetes (Centers for Disease Control and Prevention, 2020) and worsen psychological health (Luppino et al., 2010). In contrast, excessive weight loss can result in nutrient deficiencies (World Health Organization, 2021) and decreased physical and cognitive function (Grau et al., 2019). In a longitudinal study of 107 adults, Crenn et al. (Crenn et al., 2014) reported weight gain in 42% of TBI patients and weight loss in 28% of patients compared to pre-injury weight over a median period of 38 months. Hyperphagia (>2500 kcal/day) and dysexecutive syndrome were associated with a 4.5-fold and 2.5-fold increased risk of weight gain, respectively, whereas hypophagia (<1500 kcal/day) and higher pre-TBI body mass index were associated with a 4.1-fold and 4.9-fold increased risk of weight loss post-injury (Crenn et al., 2014).

Common weight management strategies include dietary modifications, regular physical activity, and behavioral interventions. However, these strategies may need to be adapted or modified for individuals with TBI based on their symptoms and capabilities. For example, individuals with physical limitations may require tailored exercise programs that accommodate their specific needs and abilities. Additionally, cognitive deficits may require visual aids or reminders to assist with meal planning and portion control. Clinicians should screen for weight changes and refer to multidisciplinary teams that include a dietitian for weight management during TBI outpatient care.

6. Gut microbiome in mTBI

6.1. Brain-gut-microbiome axis

There is a growing body of evidence showing that diet has a significant modulatory influence on the brain-gut-microbiome (BGM) axis on human health and wellness (Horn et al., 2022; Puhlmann & de Vos, 2022; Wiertsema et al., 2021). There is evidence of disruptions in the composition of gut bacteria and microbial communities (i.e., dysbiosis) associated with several neurological disorders (Morais et al., 2021). The BGM consists of three dynamic parallel and interacting communication channels implicating neural, neuroendocrine, and inflammatory signaling mechanisms (Martin et al., 2018; Mayer et al., 2022; Osadchiy et al., 2019). Given the interdependent nature of the brain-gut relationship, proposing disruptions in gut microbiome in relevant TBI populations is reasonable. Since the inflammatory processes that promote mTBI pathophysiology are also implicated in functional damage to the GI tract (Kharrazian, 2015; Sundman et al., 2017), and intestinal dysfunction is associated with a systemic immune response (Arrieta et al., 2006), it has been speculated that these interactions exacerbate neuroinflammation of compromised microglia (Sundman et al., 2017).

Soriano and colleagues provide initial evidence of changes in the gut microbiome following sports-related mTBI in four American collegiate-level football players (Soriano et al., 2022). Namely, two bacterial species known for their anti-inflammatory properties were significantly depleted (Soriano et al., 2022). Liu et al. (Liu et al., 2024) reported significant stepwise increases in alpha diversity at 1- and 16-hours post blast exposure in the blood of SMs during breacher training. Increased alpha diversity in the blood was associated with difficulty concentrating 1-hour post exposure. Significant increases in Zonulin and Intestinal-Fatty Acid Binding Protein (I-FABP), intestinal permeability biomarkers typically related to chronic inflammatory and autoimmune GI conditions at 16 hours post exposure were also observed (Liu et al., 2024). Increased Zonulin and I-FABP levels were also associated with 1-hour post exposure headache, difficulty concentrating, dizziness, and slowed thinking (Liu et al., 2024). Studies investigating the relationships among TBI, blast exposure, and changes to the gut microbiota must be replicated in larger samples to confirm findings. There is robust evidence that gut microbiota composition is correlated with depression (Huang et al., 2023; Sublette et al., 2021) and PTSD (Malan-Muller et al., 2022; Sonali et al., 2022). Continued research is needed to explore acute and longitudinal changes in gut microbiome flora associated with mTBI and relevant comorbidities in militarypopulations.

6.2. Psychobiotics

There is a growing body of evidence indicating that modulation of the BGM axis via probiotic supplementation can be used therapeutically for neuropsychiatric disorders and for improving general psychological health (Oroojzadeh et al., 2022; Ross, 2023; Smith et al., 2021; Vasiliu, 2023) and may be neuroprotective for neurologic disease (Skowron et al., 2022; Varesi et al., 2022). Some published evidence suggests that probiotics may be beneficial for treating chronic mTBI. Brenner and colleagues conducted an 8-week (+/– 2 weeks) RCT of a daily probiotic (n = 16; Lactobacillus reuteri DSM 17938) versus placebo (n = 15) supplementation with U.S. Veterans from OEF/OIF with an mTBI suffering from comorbid PPCS and PTSD (Brenner et al., 2020). The results indicate that out of a robust panel of inflammatory biomarkers, the decrease in plasma C-reactive protein approached statistical significance in the treatment group compared to the placebo group. In addition, compared to the treatment group, the placebo group showed a more significant increase in mean heartbeats per minute during the Trier Social Stress Test between baseline and the math task (Brenner et al., 2020). However, conducting similar RCTs with larger sample sizes is necessary to ascertain the effects of probiotic supplementation in treating this relevant mTBI population.

7. Special considerations

7.1. Nutrition assessment

Clinicians should first assess and intervene in the diet as a whole before considering nutritional supplements. Dietary intake can be assessed using a variety of in-person and online tools. Assessment tools include questionnaires (e.g., Block Food Frequency Questionnaire), journaling (e.g., 3–7-day food diary), an in-person 24-hr recall, Automated Self-Administered 24-hour (ASA24^®) online dietary assessment tool, and emerging technologies such as photo-based applications (see Table 1). Each of the assessment tools has advantages and disadvantages. The most viable approach for the clinician is to use the ASA24^® or obtain a 24-hour recall or three to seven-day food journal from the patient following patient education on food types and portion sizes. Doing so will provide the clinician with an understanding of general dietary patterns (e.g., meal timing, eating behaviors) and diet quality, as well as quantitative assessment of caloric and macronutrient intake. After assessment, the clinician can provide diet or supplement recommendations to the patient for therapeutic benefit or refer to a dietitian for more in-depth intervention.

7.2. Operational rations

Another consideration is the potential impact that diet may have on a patient’s TBI-related symptoms when deployed. Depending on the logistical infrastructure or the maturity of the theater of operations, deployed SMs may subsist on operational rations, ranging from shelf-stable Meals, Ready-to-Eat (MREs) to unitized group rations when field kitchens are feasible, or a combination of both (Defense Logistics Agency, 2023). Operational rations are a means to provide adequate amounts of macronutrients and energy to sustain a SM in a combat or training environment for up to 21 days (Department of the Army, 2019). The proportions of macronutrients in MREs are 13% protein, 36% fat, and 51% carbohydrates, with an overall energy content of 1,250 kilocalories per meal (Defense Logistics Agency, 2023a). Three MREs provide one day’s Military Recommended Daily Allowance of vitamins and minerals. While commanders may approve additional food supplements to enhance nutrition, the list of authorized foods for supplementation is limited in the types of fresh produce and further limited if serving fewer than 50 individuals (Department of the Army, 2019). Overall, little consideration is given to the quality of the calorie when feeding large numbers of individuals in resource-constrained environments. Anecdotally, SMs may augment their diet during training or while deployed with ultra-processed foods that they may bring to training or have mailed to them while deployed. Clinicians may consider additional nutrient supplementation in operational settings with limited access to nutritious foods.

7.3. Caffeine

There is emerging evidence that caffeine consumed via coffee may be beneficial in reducing neuroinflammation that contributes to neurodegenerative conditions such as Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, and Huntington’s disease (Ruggiero et al., 2022). However, the impact of caffeine on rehabilitation from mTBI sequela remains unclear. Caffeine may cause adverse side effects, such as feeling “jittery or shaking,” palpitations, sleep disturbances, and dehydration (Johnson et al., 2014), potentially producing or exacerbating TBI-related symptoms, and altogether discontinuing caffeine intake may lead to withdrawal headaches and brain fogginess – all of which may complicate the mTBI evaluation. The VA/DOD mTBI guidelines advise minimizing caffeine and avoiding herbal or dietary “energy” supplements during the post-acute TBI phase (The Management and Rehabilitation of Post-Acute Mild Traumatic Brain Injury Work Group, 2021).

7.4. Alcohol

The evidence on the effect of alcohol on TBI recovery is mixed and results vary based on the level and timing of consumption related to the TBI event. Although acute alcohol intoxication has been shown to increase the risk of TBI (Weil et al., 2018), the studies on evaluating the association between acute intoxication at the time of injury and long-term clinical and functional outcomes have had mixed findings (Booker et al., 2019a, 2019b; Silverberg et al., 2016; Scheenen et al., 2016). Evidence supports that alcohol use decreases in the sub-acute period post-injury (Silverberg et al., 2016; Weil et al., 2018), whereas post-injury alcohol consumption has been linked to protracted recovery with a mean of 5.6 days longer to return to unrestricted play (Chang et al., 2022). Results concerning long-term clinical and functional mTBI outcomes and their relationship to pre-injury alcohol use are also varied (Silverberg et al., 2016; Theadom et al., 2016). Whether or not mTBI is an independent risk factor for alcohol use disorder remains inconclusive, although the association in SMs has been observed at the population level (Johnson et al., 2015; Weil et al., 2018). Clinicians should consider evaluating the patient’s drinking behaviors at each visit, screen for alcohol use disorders, and discourage alcohol consumption until symptoms have resolved (The Management and Rehabilitation of Post-Acute Mild Traumatic Brain Injury Work Group, 2021).

8. Conclusion

Nutrition intervention through a whole diet or nutritional supplementation is an emerging area of interest in mTBI and overall brain health. Studies demonstrating the association of dietary inflammatory potential with conditions that commonly co-occur with mTBI (e.g., depression and PTSD) have laid the groundwork for future hypothesis-driven research that will lead to a better understanding of the role of diet in mTBI. The military food environment, both in training and austere setting, presents a unique consideration for the clinician providing dietary guidance during mTBI rehabilitation. The evidence supporting a specific diet or supplementation regimen to enhance neuroprotection or mitigate mTBI symptomology in humans is not yet strong enough to formulate clinical guidance; however, dietary supplementation with nutrients discussed in this article as having potential benefit in TBI (e.g., omega-3 fatty acids, creatine, and vitamin D) is generally safe when taken within recommended guidelines. Additionally, the DOD’s Warfighter Nutrition Guide recommends eating a diverse, high-quality diet that includes colorful whole foods rich in antioxidants, phytonutrients, omega-3 fatty acids, micronutrients, probiotics, and sufficient fiber to optimize long-term health and performance (Consortium for Health and Military Performance, 2022). Although the evidence surrounding nutrition’s role in the modulation of mTBI pathophysiology in preclinical models is promising, more research is needed to determine the clinical effects of nutrition interventions for mitigating mTBI symptoms, common comorbid conditions, and associated long-term health sequelae. Future studies should evaluate the relationship between dietary inflammatory potential and TBI-related neurobehavioral and psychiatric outcomes. Further, due to both the substantial variability in human responses to nutrients and the complexity of mTBI pathophysiology, a precision medicine approach is necessary in order to produce efficacious dietary interventions for TBI.

Funding

The study was supported under Contract HT0014-22-C-0016.

Declarations of interest

The authors have no declarations of interest.

Disclaimer

The views expressed in this manuscript are those of the authors and do not necessarily represent the official policy or position of the Defense Health Agency, Department of the Army, Department of Defense, or any other U.S. government agency. This work was prepared under Contract HT0014-22-C-0016 with DHA Contracting Office (NM-CD) HT0014 and, therefore, is defined as U.S. Government work under Title 17 U.S.C.§101. Per Title 17 U.S.C.§105, copyright protection is not available for any work of the U.S. Government. Material has been reviewed by the Walter Reed Army Institute of Research. There is no objection to its presentation and/or publication. The investigators have adhered to the policies for protection of human subjects as prescribed in AR 70–25. For more information, please contact dha.TBICOEinfo@health.mil, UNCLASSIFIED.