Jen Hatz MS, RD, CSSD, LDN, CSCS
Before the discovery of unique structural changes in the brain of a former athlete, and the subsequent surge in research identifying these structural changes in the brains of other former athletes post-mortem, the concept of encephalopathy resulting from repeated damage to the brain was an otherwise unknown or undisclosed reality. What is even more interesting however, is that research has uncovered these structural changes in the brains of non-athletes, and in those who did not meet the prototypical criteria of damage to brain cells from concussions, TBI, or repeated head injuries. (Bieniek, et al. 2020)
In fact, research began to uncover more about this lingering and undisclosed condition by exposing us to the reality that structural changes in the brain could occur regardless of head impacts like from sports concussions or head injuries, as well as the converse that functional changes in the brain can occur involving drastic changes in mood, behavior, emotional processing, impulse control and decision-making without any structural changes. (McKee, et al. 2023) This stark contrast and lack of direct relationship between structural changes and functional changes (or the "symptoms" experienced) points us to new view of this domain entirely: redefining how we view "changes in the brain" and how we understand "chronic trauma".
A recent study exposed this new view of CTE, allowing us to widen our lens of how we view brain functioning and mental health, particularly in young adults and in those who participated in athletics. In this study of collision sport athletes, across 152 brains of former athletes who died before the age of 30, where the top two causes of death were suicide and unintended overdose, there were mild structural changes characteristic of CTE in 40% of those donated brains. (McKee, et al. 2023) This figure is meaningful considering that the young ages of these former athletes at the time of death illustrates structural changes occurring, and even so across different sports including football, soccer, hockey, rugby, and wrestling, as well as duration of athletic career with particular emphasis in amateur or collegiate-level athletics. (McKee, et al. 2023)
What is even more meaningful is the fact that 60% of these brains did not show any structural changes worthy of a CTE diagnosis, those that did showed a mild state, and yet 100% of these former athletes met the same outcome: an early death due primarily to escaping the life they are experiencing, whether intentionally or not. This points to a large paradigm shift with viewing chronic trauma in athletic populations, and in young adult populations, where there are likely multifactorial points of potential trauma, stress, and physiologic changes occurring with an emphasis on the function of these brains, independent of structural changes.
Add to this the fact that the majority of donated brains were reported as male with racial identity as White (73%), with 17.8% reported with racial identity as Black, yet those with diagnosed CTE were more likely to have Black racial identity, older age, and more years in total playing football, with no difference based on position played. (McKee, et al. 2023) This distinction is noteworthy and should not go unnoticed as it highlights a very real, and potent, magnitude of trauma expressed in the brains of these individuals across life.
This paradigm shift means we broaden our view of the brain to encompass also the function of the mind, of perception, behavior, motivation, and decision-making into the story of everyday life and lifestyles. We can no longer rest of the notion that repeated head injuries are the only lifestyle factor impacting the health of these young athletes' brains, but rather a more complex and multidisciplinary cross-section of varying layers of stress and trauma experienced across their life, and across their lifestyle.
What if we expand our view of CTE, or chronic traumatic encephalopathy, beyond solely structural changes diagnosed post-mortem, but rather to encompass the impact of neuroinflammation, oxidative stress, and changes in brain metabolism and blood-brain barrier function all occurring in response to chronic trauma during life. This requires our further expansion in redefining "chronic trauma" to encompass the variety of forms and layers of trauma that an individual can experience including physical, psychological, and physiological trauma where the body and brain exhibit changes due to experiencing danger, whether physical, psychological, or physiological that is beyond our capacity to handle or that is otherwise unexpected or unwarranted for a given environment of situation.
The important questions to ask revolve around identifying sources of trauma that an individual may be exposed to that result in neuroinflammation, oxidative stress, and an impaired blood brain barrier and brain metabolism, independent of physical impacts.
Once we identify sources of trauma and the impact they have on the body and brain, then we can work towards healing, resolving, and strengthening resilience. This involves continual monitoring and assessing of physiological cues through biomarkers, biofeedback, and neurofeedback with psychological cues through changes in decision-making, perception, mood, and behavior, all while making adjustments across our intake patterns and actions including nutrition and hydration, sleep behavior, environmental factors, use of substances, social, spiritual, and community engagement, and more.
Viewing trauma through this expanded lens, and allowing for a holistic view of the variety of ways in which trauma is expressed through the body and brain by exhibiting a chronic response to danger, we can then make steps in identifying sources of danger, and work to limit the trauma experienced in our brain and body, as we ultimately change and transform the ways in which we function, including how our brains function and perceive reality.
Getting into the science of CTE:
While there was a popularized theory that concussions specifically played a role in CTE-related neurodegeneration, our understanding of concussions is still poorly defined and understood, to where we now accept the notion that structural changes occurring in CTE are not specific to concussions per se, but rather as a consequence to brain trauma, however large or small. (Tharmaratnam, et al. 2018) Today we define CTE to include any repetitive, episodic, or single precipitating event that leads to progressive neurodegeneration in the brain, most notably as structural and metabolic changes in the axon in response to injury. (Tharmaratnam, et al. 2018) Think of it this way: even the slightest degree of trauma destabilizes this precious brain tissue causing an immediate hyper-response of accumulating p-Tau proteins to stabilize the cell, which form along the inside of the axon and form tangles over time. These tangles forming along the inside of the axon is a major reason why this condition cannot be detected visually from a typical scan (PET scan) that would otherwise be able to identify other structural changes like in Alzheimer's disease where the b-amyloid plaques aggregate in the spaces surrounding the outside of the cells, making it visible in a scan. Once these tangles (called neurofibrillary tangles, or NFT) form within the axon, they interfere with signaling and communication and ultimately propagate further tau accumulation, as if the axon can be described as "being strangled from the inside out".
**And now we expand our view of "trauma" or "precipitating events" to include multifactorial exposures and experiences of stress to the brain which can be physical, psychological, or physiological in nature.
Because the actual cell trauma is only part of the equation...
It's ultimately the neuroinflammatory response that leads to oxidative stress and free radical accumulation, upregulated metabolic processes, mitochondrial dysfunction, and calcium imbalance (which impacts signal transduction), ultimately causing hyperphosphorylated tau (like an uncontrolled forest fire). (Tharamaratnam, et al. 2018) While we may want to assume that head injury frequency and severity is the largest risk factor, the reality is that CTE is observed in both athletes and non-athletes, and in those with significant history of head injuries as well as those without, and even individuals who have significant history of head injuries do not necessarily develop this neurodegenerative disease. (Tharamaratnam, et al. 2018) This implies that there are likely genetic and lifestyle factors that play a role in disease progression where for example there is evidence to suggest an increased risk for individuals with a Apoe4 allele that can impact cholesterol transport in the brain used for repairing neurons. (Tharmaratnam, et al. 2018) The age when starting tackle football has been associated with increased risk later in life (specifically starting football before 12 years old was associated with more than double the risk of cognitive impairment later in life), possibly due to multifactorial points of neurological maturation at that age affecting the vulnerability of the brain tissue, longer overall length of time playing shows increased risk for greater frequency and severity of head injuries, and the longer an athlete is associated with a sport as part of his lifestyle and identity, the more difficulty there may be with transitioning to a lifestyle that no longer involves physically playing the game. (Tharamaratnam, et al. 2018)
**This is a key point of our attention and focus: if playing a sport (specifically a dangerous sport, and playing competitively) means you are physically, psychologically, and physiologically experiencing a heightened degree of danger beyond what would be considered normal or normal duration for our physiology, your body and brain will therefore exhibit those effects of chronic trauma. This concept translates for tactical populations as well including military personnel, first responders, and those in positions of heightened stress. Real or perceived danger of trauma can magnify when engaging in a dangerous sport or occupation, where the effects of "survival instincts" in performing work may compound with the effects of operating in "survival mode" across lifestyle factors of high stress, poor sleep, socio-economic factors, and demographic inequities accumulating across years of an unstable and unsustainable lifestyle.
What can we start to look for?
The presence of frequent low-grade inflammation and cell damage to brain tissue takes on new meaning when we begin to identify functions of our mind and mental health with behaviors and decisions we engage in, with items we take in whether physically digesting and absorbing or psychologically, and with downstream effects that impact our gut barrier, our blood-brain barrier, systemic inflammation, neuroinflammation, and our overall stress response through autonomic and neuroendocrine signaling.
The big 3 factors to look at include:
Sleep: sleep is the physiological state of repair and recovery to brain tissue and body tissue where sleep deprivation, or even sleep deficits below the needs of the individual, can be associated with impaired physiologic and psychological functioning. There are research findings highlighting a link between REM sleep behavior disorder and tau protein pathology like that of CTE. (Adams, et al. 2020) We want to monitor for sleep disturbances, particularly REM sleep disturbances like acting out dreams, kicking, talking, reacting, or physical agitation during REM sleep.
Alcohol: alcohol use induces damage to the brain and is a strong predictor of worsening effects, cellular damage, and oxidative stress impacting injured brain tissue or cells requiring recovery and repair due to factors of stress and trauma. (Weil, et al. 2018) We want to monitor for any alcohol intake across any volume and any frequency.
Blood glucose (Blood-brain barrier and blood glucose control): insulin resistance within the brain is termed as Type III diabetes and is related to neuroinflammation and impaired blood-brain barrier where resulting inflammation and oxidative stress can occur due to excessive insulin exposure. (Michailidis, et al 2022) Insulin is released from the pancreas and normally affects neurotransmitters and long term memory when crossing an intact blood-brain barrier, however when this barrier is impaired, insulin passes through at higher than normal concentrations and rates, and can impact tau protein pathology and b-amyloid accumulation with subsequent neuroinflammation. (Michialidis, et al. 2022) Consequently, in Alzheimer's disease, increased β-amyloid antagonizes insulin and IGF-1 receptor binding, which increases inflammation and triggers the onset of insulin resistance. (Michialidis, et al. 2022) When insulin dysfunction and inflammation combine with oxidative stress, there is enhanced toxicity and concentration of β-amyloid in a pathological feedback cycle. In this sense, the dysregulation of insulin signaling affects the metabolism and function of the cells, leading to the accumulation of tau protein in the cell, which is a major cause for neurodegeneration. (Michailidis, et al. 2022) We want to monitor for BBB integrity and function, with blood glucose monitoring and gut barrier integrity.
Let's break this down:
An impact causing damage, whether large or small, physical, psychological, or physiological, is a momentary event. Yet it is the ongoing aftermath with accumulation of byproducts, end-products, and impaired metabolic processes that create a lasting trauma to the cell, and continue the cycle so that those singular moments in time of impact creates an endless effect of trauma systemically and longitudinally.
Metabolic processes in the brain are ongoing regardless of the environment or circumstances present which indicates a constant source of potential downstream effects from damaging events. In fact, metabolic processes increase at a rapid rate in response to trauma, or any real or perceived threat, as a method of stabilizing the cell with upregulated metabolic processes intended to protect and recover from damage yet the upregulation of metabolism could be increasing the degree and severity of cell damage through this cascade of effects.
What's more noteworthy, during periods of stress or trauma, and in the presence of impaired blood-brain barrier and neuroinflammation, the presence of oxygen used for cell metabolism may exacerbate oxidative stress with the cells relying on anaerobic processes (being able to convert energy without oxygen present) in addition to an increased energy demand to immediately protect and quickly repair those precious cells. Creatine is your first energy substrate that you will rely on, as well as glucose (carbohydrate) that is being metabolized anaerobically. Under conditions of anaerobic carbohydrate metabolism, lactic acid accumulates, cellular pH drops, enzymes no longer function at their capacity and the process essentially shuts down, accumulating byproducts that can spill over causing further cell damage.
In fact, the increased energy demands, shift in metabolic processing with toxic byproducts accumulating, and the impaired cell structure and function from progressive changes over time (like with prolonged exposures, more years playing, etc) impairing insulin signaling, create a complex web of repeating traumatic damage.
What can we do to start addressing it now?
As much as this contradicts advice and recommendations across sports nutrition, the reality is having an athlete ingest a high concentration, high glycemic load across their diet and particularly before, during, and immediately after their training conditions could be causing harm. A dialed down approach of fiber rich carbohydrates to naturally slow down the rate of digestion and absorption should be prioritized, and with efforts across healing and repairing gut barrier integrity, and reducing inflammation, can coincide with addressing blood-brain barrier integrity.
Alcohol intake likewise exhibits damaging effects to brain tissue creating worsening effects on metabolic processes with excessive inflammation and oxidative stress. Any amount of alcohol ingestion should be recommended against, particularly in protecting the barrier functions across the gut-brain axis as well as protecting the mental health and cognition of individuals regardless of the quantity or rationale for drinking alcohol.
Sleep should be prioritized across the lifestyle and with accommodations made on a nightly basis to ensure individualized sleep needs are met regardless of location or schedule changes.
Creatine supplementation should be emphasized as a daily staple, with increased dosing during periods of recovery from any concussive event or injury.
An additional note to keep in mind, if we look at the fueling and hydration practices for sports, especially across the most recent decades:
Typically low fiber foods are emphasized, particularly during and around training and competition, leaving less opportunity in daily eating to take in the amount of fiber that is actually needed in exchange for high calorie and simple carbohydrate intake. **This recommendation against fiber intake needs to be revisited and revoked to instead optimize fiber intake over refined carbohydrates in order to optimize the rate of absorption along the GI tract and to support gut microbiome and barrier function to limit rapid increases in blood glucose concentrations.
Juices, juice-based drinks, and sports drinks are used excessively, across the diet, and particularly during the immediate and post-workout window of time when GH and IGF-1 have the largest daytime spike. **This recommendation, while well-intentioned to rapidly restore muscle glycogen during this window of time, may need to be revoked entirely if findings suggest that insulin dysfunction within the brain is implicated and impacted.
On-field fueling and hydration has historically been synonymous with a one-size-fits-all approach of sports drinks being readily available and anything that emphasizes quick digesting, high glycemic carbohydrates. **These recommendations need to be revisited and adjusted to individualized needs based on context with a priority on the athlete's health and clinical assessment.
**These practices, while intended to provide fueling and hydration, may in fact be more harmful than beneficial. Research shows that of the variety of drinks from hypotonic, to isotonic, to hypertonic, that it is hypotonic beverages of oral-rehydration-solutions like Pedialyte that are beneficial for hydration and thermoregulation whereas isotonic beverages like sports drinks and hypertonic drinks like high sugar energy drinks are worse. (Rowlands, et al. 2022)
When combining risk factors like high glycemic intake across low fiber foods and high sugar drinks, sports drinks impairing hydration status and thermoregulation, as well as impaired metabolic processes in the brain with chronic inflammation and oxidative stress having a direct and immediate impact on carbohydrate metabolism, the degree of damage and trauma to the body and brain can become excessive. Even worse, accumulation of those tau proteins over time, as part of the natural inflammatory recovery response to trauma, interfering with insulin signaling can lead to excessive damage more rapidly accumulating in response to these lifestyle factors. This may indicate why there is a reported sudden onset of symptoms that rapidly worsen if we view a lifestyle across nutrition and hydration, alcohol ingestion, and sleep disturbances all adding fuel to a fire that is burning beneath the surface and where a longer duration career featuring these variables can expedite the structural changes occurring in the brain.
References:
Adams, J.W., Alosco, M.L., Mez, J. et al. Association of probable REM sleep behavior disorder with pathology and years of contact sports play in chronic traumatic encephalopathy. Acta Neuropathol 140, 851–862 (2020). https://doi.org/10.1007/s00401-020-02206-x
Bieniek, K.F., Blessing, M.M., Heckman, M.G., Diehl, N.N., Serie, A.M., Paolini, M.A., II, Boeve, B.F., Savica, R., Reichard, R.R. and Dickson, D.W. (2020), Association between contact sports participation and chronic traumatic encephalopathy: a retrospective cohort study. Brain Pathol, 30: 63-74. https://doi.org/10.1111/bpa.12757
McKee AC, Mez J, Abdolmohammadi B, et al. Neuropathologic and Clinical Findings in Young Contact Sport Athletes Exposed to Repetitive Head Impacts. JAMA Neurol. 2023;80(10):1037–1050. doi:10.1001/jamaneurol.2023.2907
Michailidis, M., Moraitou, D., Tata, D. A., Kalinderi, K., Papamitsou, T., & Papaliagkas, V. (2022). Alzheimer's Disease as Type 3 Diabetes: Common Pathophysiological Mechanisms between Alzheimer's Disease and Type 2 Diabetes. International journal of molecular sciences, 23(5), 2687. https://doi.org/10.3390/ijms23052687
Rowlands, D. S., Kopetschny, B. H., & Badenhorst, C. E. (2022). The Hydrating Effects of Hypertonic, Isotonic and Hypotonic Sports Drinks and Waters on Central Hydration During Continuous Exercise: A Systematic Meta-Analysis and Perspective. Sports medicine (Auckland, N.Z.), 52(2), 349–375. https://doi.org/10.1007/s40279-021-01558-y
Tharmaratnam T, Iskandar MA, Tabobondung TC, Tobbia I, Gopee-Ramanan P, Tabobondung TA. Chronic Traumatic Encephalopathy in Professional American Football Players: Where Are We Now?. Front Neurol. 2018;9:445. Published 2018 Jun 19. doi:10.3389/fneur.2018.00445
Weil, Z. M., Corrigan, J. D., & Karelina, K. (2018). Alcohol Use Disorder and Traumatic Brain Injury. Alcohol research : current reviews, 39(2), 171–180.