It was a moment that every kid has dreamed of: preparing for (what I felt like at the time) was the biggest game of my life with some of my best friends and teammates. It was a cold, snowy night in December at MetLife stadium, home of the New York Giants. We were competing for the high school football championship against our much bigger rivals, Mountain Lakes. My 165-pound self (though the stats books claimed I was 185 pounds) decided to be “tough” and not wear sleeves for what felt like the coldest day of my life.
Friends, family, and loved ones lined the stands at the stadium to cheer us on despite freezing themselves. As I walked out for the first play on defense, I remember looking up and thinking, “Is this real life? Are we really playing on the same field that the New York Giants play on right now?” And then, the first play happened… Let me again preface this by saying that Mountain Lakes was a much “bigger” team; in a sense, it was like watching men vs. boys. Their 215-pound running back, 270-pound lineman, and quarterback who went on to play for a top Division I college were our toughest opponents yet.
It was the first play of the game. The ground was rock hard, and slush lined the field, so running the ball seemed like the best option. We were in a “Cover 3,” and I was playing safety. Toss left. Our defensive end got blocked, our linebacker slipped and lost his footing, and our cornerback couldn’t get off a block either. I read the play and made a dash towards the sideline to cut the running back off. At this point, I was the last line of defense. I could see him clearly. I thought, “I’m definitely going to tackle this guy,” “truck-stick” him nonetheless, to send a message. And then…. WHAM!! The next thing I knew, I was lying on the ground looking down the sideline as the running back ran into the end zone for a touchdown. It was the first play of the game, and they scored a touchdown. Some of my teammates came over to help me up, and I soon realized that something wasn’t right.
Not only could I not feel my right shoulder, but I was dizzy and couldn’t put much pressure on my right leg. It wasn’t until I was over at the sideline that I found out that not one but two of the 270-pound lineman came around, and blocked my 165-pound scrawny self from the side to spring the running back into the end-zone. Needless to say, I was hurting bad, and the game had just begun. Our trainer looked at me and said, “you have two options: either you can come out of the game and we can get you rested for basketball season, or we can do what we can to make sure you can finish out this last game.” No brainer. Five minutes later, I felt like a science experiment with a wrap extending from my shoulder down to around my leg and knee. I had torn my MCL, gotten a bad stinger, and without a doubt suffered some serious head trauma from the hard hit straight on the ground. Eight aspirin later, a correct guess at some fingers he was holding up, and I made my way back out on to the field.
We ended up getting blown out and lost by a large margin, but nonetheless it was an incredible experience. I planned to be sidelined from basketball (basketball season started the following week) for several weeks after in order to rehab my MCL, but that wasn’t even the major setback for me. No one other than my parents knew at the time that I could hardly sleep at night, had constant headaches, and frequently left class due to nausea and eventual vomiting throughout the next week. Looking back, there was no doubt that I had a concussion/mild TBI following that game. That wasn’t the first time I had experienced a concussion throughout my young career, but it was the one that was most vivid for me.
The reason for this article isn’t to relive the glory days and talk about some of my high school memories but rather to talk about how quick and easy it is to get a concussion, how easily it gets overlooked, and, knowing what I know now, how to determine if I could have done anything differently. For anyone who knew me in high school, I was the biggest “carbaholic”. I ate 4 bowls of cereal for breakfast, a school lunch plus a weight gainer shake (I was trying to bulk up that 165-pound frame) and usually a nice Italian dinner at night (thanks Mom ). If time spared me, I would eat a sleeve of Oreos before bed…literally an entire sleeve. Thus, the concept of a ketogenic diet was nowhere near my radar nor had I ever heard, read, or seen anything even remotely close to the concept. At that time, the only answers I got from my doctors, my trainers, and even my parents were simple: rest and Advil. However, if I could go back and do it all over again, is there anything I would have done differently? How could I take what I know now and let 17-year-old Ryan know that there might be a different way he could deal with that traumatic brain injury (TBI)?
Altered Brain Metabolism
Dr. Bennet Malu, or as some of you may recognize as the actual person who Will Smith portrayed in the movie Concussion, closely examined the brains of several football players and discovered that they had severe brain damage reminiscent of patients with Alzheimer’s disease. Specifically, these individuals had the buildup of beta amyloid plaques and neurofibrillary tangles (1). You can see where this is going…
TBI is a leading cause of death and disability in infants (<2 years) and adolescents (15-18). Additionally, over 20% of the pediatric patients who have suffered a TBI experience lifelong physical disabilities such as “cognitive impairments with persistent attention, memory and concentration deficits as well as emotional disorders such as anxiety and depression, which can significantly influence academic and work performance and cause profound social dysfunction later in life” (2). The financial burden alone is alarming. The US spends about 1 billion per year just in pediatric TBI patients. That's just a fraction of what the NFL is expected to pay out in their recent settlement with former players who are now experiencing long term effects or even chronic Traumatic Encephalopathy (CTE) is a progressive degenerative disease of the brain found in individuals with a history of repetitive brain trauma, including symptomatic concussions as well as asymptomatic sub-concussive hits to the head.
Just recently, a study was published looking at repetitive head impacts (RHI) and cognitive function in youth athletes (3). To put this in perspective, worldwide more than 22 million children and adolescents are exposed to RHI’s in soccer alone. On average, soccer players perform 6-12 headers per game, and many more during practice, resulting in thousands of headings over a player’s career (3). This study looked at a group of 15-year-old male soccer players cognitive function throughout the entire season. They found an association between exposure to specific RHI (long headers) and lack of improvement in cognitive performance in youth athletes over time. Additionally, the kids who performed the most long headers had the lower his improvement in reaction time over the course of the study.
Traumatic brain injury (TBI) occurs as the consequence of a direct or indirect mechanical force applied to the head. Following a concussion or blow to the head, there is an initial insult to the brain; however, many of the adverse effects we see may be caused by secondary injury or events that take place long after the initial hit or insult happened. How could this be?
Following a concussion, the brain has an increased demand in energy. This makes sense in that the brain is doing its best to increase energy uptake to recover and overcome the repeated blows or blow that it has taken. However, there is one slight problem…the brain also has an impaired ability to take up glucose during this time. Wait a minute. At the time when our brains need energy the most, we have an inability to take up glucose to provide that energy, so what do you think happens? This is where those secondary or longer term injuries can start to take place, such as inflammatory changes, vascular changes, edema (swelling), and even free radical formation, which all can lead to damaged DNA, proteins, and increased cell death.
We should be able to rebound quickly after these insults, right? Not necessarily. In fact, after the initial period, brain glucose use is diminished for 24 hours post-injury and remains low for 5 to 14 days on average and at times for months depending on the severity of the injury (4). These levels of depressed glucose metabolism are strongly associated with cognitive impairments (5). Clearly our brains don’t enjoy dealing with these types of impairments and blows to the head that frequently take place in various sports and situations. The question becomes: can our body adapt to utilizing a different fuel source for energy during this critical time of need, or are we just stick trying to wait on the “slow drip” glucose to try and make itself into the brain?
Ketosis and TBI
TBI results in impaired brain energy metabolism. What if there was an alternative source of fuel that could be used during this time? In fact, what if our brains automatically increased the transporters necessary to take up more of this alternative fuel source during this dire time of need? There is an alternative source of fuel, and it is a fuel that our body is well equipped to use, yet we seldom allow it to do so.
It is known that both rats and humans are ketotic when born and therefore rely heavily on ketones for fuel (6). Thus, from the start, our bodies have the ability to take up and utilize ketones as a source of fuel. This means that there are certain transporters or tunnels that can take ketones into the brain and various other tissues for us to use them during times of starvation or when carbohydrate levels in the diet are low (e.g. during a ketogenic diet). However, as we age, it is possible that these transporters or tunnels decrease due to the nature of our diet (eating carbohydrate-rich foods, always snacking, etc.).
Prins and Giza (7) found that following a TBI, certain transporters (or tunnels) that take up ketones into the brain are increased. It is almost as if our bodies understand there is a need to get an alternative source of fuel to the brain. Thus, to help take up ketones for fuel, it is plausible that MCT2 tunnels become upregulated. Even though the transporters are elevated, many athletes and individuals tend to consume sugar-rich sport drinks or carbohydrate-containing foods, so it is as if tunnels are wide open but no cars are driving through (i.e. ketones aren’t going through the tunnel transporters).
There are at least 4 different ways that ketones may be beneficial to TBI.
Back in the early 2000s, studies showed that infusing ketones (BHB) following a TBI in an adult rat resulted in improved ATP (energy) concentrations (11). Future studies built on this work by placing adolescent and adult rats on a ketogenic diet either 1 week before or immediately after experimentally induced TBI. The ketogenic diet decreased the size of the lesions in the brain, improved cognitive and motor function, and decreased cell death (12,13). Without going into too much detail, there are differences between how younger and older animal respond, primarily because adolescent mice have been shown to have over 80% more of the ketone transporter proteins than older adults. However, studies have shown that exercise can actually increase these transporters along with longer duration ketogenic diets. Therefore, it may be that as we get older, a combination of exercise, ketogenic dieting, periodic fasting, and exogenous ketones may be necessary to elevate ketones to a level adequate to overcome the energy deficit following a TBI.
Advice to Younger Ryan
By no means am I a medical doctor nor do I intend to give medical advice. Instead, this is a memoir to my former self on what I would have done now that I understand the research behind TBIs. Had I known what I know now, I would have implemented some strategies to allow me to potentially overcome some of those rough days and weeks following that big blow. First and foremost, I would have been fasting. Studies have shown that fasting animals for 24 hours after a trauma resulted in a significant increase in tissue sparing (lowered oxidative stress), neuroprotection, cognitive function, and mitochondrial function (14). Additionally, I would have supplemented with exogenous ketones during this time had they been available. Ideally I would opt for one that is efficaciously dosed and elevated ketone levels to a point in which they could be utilized and taken up the brain. Lastly, I would have lowered my carbohydrate intake and gone on a ketogenic diet following the game and incorporated periods of intermittent fasting. Ideally this would have occurred prior to the trauma, so that I would have been keto-adapted. However, my carbohydrate-addicted self would have not seen a reason why I needed to give up my morning cereal and Yoohoo prior to an incident like this.
It is clear that a TBI results in an energy crisis in the brain and impaired metabolism immediately and for up to several months following the insult. Research suggests that correcting the energy crisis may assist in recovery from the insult and may restore cellular energy to the brain. Adolescents placed on a ketogenic diet before and following injury may benefit tremendously. However, adults seem to need a longer period of time on the diet to increase the “tunnels” (MCT1, MCT2 transporters) and ketone production. As a protective measure, adults may need to keto-adapt for a longer period of time even prior to receiving TBI. For this reason, it may be efficacious for athletes in contact sports to consider being on a ketogenic diet more permanently. More recent articles are showing that once keto-adapted, performance does not appear to be impaired, even in high level CrossFit athletes.
Research with TBI and other neurological disorders like Alzheimer’s, Parkinson’s, etc. all seem to tie back to impaired brain energy metabolism (primarily derived from an inability to effectively utilize glucose). The current rates of concussions and TBI in sports are certainly alarming, and no one is more aware of this problem than the NFL. The current NFL settlement results in hundreds of millions if not billions of dollars being paid to former NFL athletes who have experienced brain trauma and are dealing with the repercussions and aftermath, or as some call it, “life after the game.” There is a strong interest from the NFL in ways in which these injuries could be minimized prior to, during, and following incidence. We are excited about some potential research and collaborations that we have been discussing with many of these organizations to test novel strategies in athletes in the near future. At the end of the day, if we could save just one kid, one son, one father from the aftermath and repercussion of something as brutal as CTE, then it is all worth it.
- Omalu, B. I., DeKosky, S. T., Minster, R. L., Kamboh, M. I., Hamilton, R. L., & Wecht, C. H. (2005). Chronic traumatic encephalopathy in a National Football League player. Neurosurgery, 57(1), 128-134.
- Aleksandra, I., Rodriguez-Grande, B., Bar, C., Villega, F., Konsman, J. P., & Badaut, J. (2017). Vascular impairment as a pathological mechanism underlying long-lasting cognitive dysfunction after pediatric traumatic brain injury. Neurochemistry International.
- Koerte, I. K., Nichols, E., Tripodis, Y., Schultz, V., Lehner, S., Igbinoba, R., ... & Kaufmann, D. (2017). Impaired cognitive performance in youth athletes exposed to repetitive head impacts. Journal of Neurotrauma, (ja).
- Hovda, D. A., Fu, K., Badie, H., Samii, A., Pinanong, P., & Becker, D. P. (1994). Administration of an omega-conopeptide one hour following traumatic brain injury reduces 45calcium accumulation. In Brain Edema IX (pp. 521-523). Springer Vienna.
- Barkhoudarian, G., Hovda, D. A., & Giza, C. C. (2011). The molecular pathophysiology of concussive brain injury. Clinics in sports medicine, 30(1), 33-48.
- Cotter D. G., d’Avignon D. A., Wentz A. E., Weber M. L., Crawford P. A. 2011. Obligate role for ketone body oxidation in neonatal metabolic homeostasis. J. Biol. Chem. 286: 6902–6910.
- Prins, M. L., & Giza, C. C. (2006). Induction of monocarboxylate transporter 2 expression and ketone transport following traumatic brain injury in juvenile and adult rats. Developmental neuroscience, 28(4-5), 447-456.
- Veech, R. L., Chance, B., Kashiwaya, Y., Lardy, H. A., & Cahill, G. F. (2001). Ketone bodies, potential therapeutic uses. IUBMB life, 51(4), 241-247.
- Ziegler, D. R., Ribeiro, L. C., Hagenn, M., Siqueira, L. R., Araújo, E., Torres, I. L., ... & Gonçalves, C. A. (2003). Ketogenic diet increases glutathione peroxidase activity in rat hippocampus. Neurochemical research, 28(12), 1793-1797.
- Youm, Y. H., Nguyen, K. Y., Grant, R. W., Goldberg, E. L., Bodogai, M., Kim, D., ... & Kang, S. (2015). The ketone metabolite [beta]-hydroxybutyrate blocks NLRP3 inflammasome-mediated inflammatory disease. Nature medicine, 21(3), 263-269.
- Massieu, L., Haces, M. L., Montiel, T., & Hernandez-Fonseca, K. (2003). Acetoacetate protects hippocampal neurons against glutamate-mediated neuronal damage during glycolysis inhibition. Neuroscience, 120(2), 365-378.
- Biros, M. H., & Nordness, R. (1996). Effects of chemical pretreatment on posttraumatic cortical edema in the rat. The American journal of emergency medicine, 14(1), 27-32.
- Appelberg, K. S., Hovda, D. A., & Prins, M. L. (2009). The effects of a ketogenic diet on behavioral outcome after controlled cortical impact injury in the juvenile and adult rat. Journal of neurotrauma, 26(4), 497-506.
- Davis, L. M., Pauly, J. R., Readnower, R. D., Rho, J. M., & Sullivan, P. G. (2008). Fasting is neuroprotective following traumatic brain injury. Journal of neuroscience research, 86(8), 1812-1822.