Ketones, TBI, and brain function

I'm not a doctor of any sorts.  Hell, I didn't even stay at a Holiday Inn Express last night.  In fact, on my trip back home to see my family we ended up staying at the Hampton Inn on two separate occasions (which promoted fat baybay to say on the drive home "we better not stay at another freaking Hampton Inn!").

Nevertheless, I read an enormous amount of studies and research articles to do my best at understanding the various facets of hypertrophy, nutrition, and of course as of late, all the benefits that come with the intake of exogenous ketones.

I've documented much of the success I've had with them in regards to physique competitors in the depleted stages of contest prep.  I've used them to help people get over nagging injuries, and even helped people overcome hypoglycemia with them.

But as of late, the one area I've spent the most time reading about in regards to them, is how they function in regards to those that have suffered a traumatic brain injury, or TBI.

The reason for this is because it has become a serious issue with players in the NFL.  And from my outside view, the league has done very little to actually address the seriousness of the issue.

Let me be clear here about one of my biggest problems with the NFL before I delve into this.

I abhor the NFL's policies on performance enhancement drugs.  But all the while having no problem prescribing narcotic drugs to their players, some of who end up with serious addiction and dependency issues on them well after their careers are over.  I'm going to put on my tin foil hat here and just take a stab that the NFL somehow is in cahoots with big pharmacy from a financial perspective.  I mean it just makes too much sense to me.

We can't have players taking growth hormone, or peptides.  Which have been proven to speed up healing and would get them back on the field faster.  But it's fine to load them up with a various cocktail of drugs that numb them down but don't actually address the problem causing the pain.  Players know their livelihood depends on playing, and playing at a high level.  So they will do whatever it takes, and play through a litany of injuries to keep their jobs because they are all aware that their time in the league most likely, is going to be very short lived.  The average NFL career I believe, is a little less than three years.  So if a guy is always in the trainers room, he won't be on the roster for very long.

The NFL has made some rules now about players and concussions.  As they are required to leave the field and get clearance before they can return to play.  However, even if the doctor rules they can't return to play that day, it doesn't take away the fact that the player is going to deal with the aftermath of said concussion.

Even worse, by the time a guy reaches the NFL, it's very likely he's already suffered concussions all the way from high school, through college.

There's actually a list of former players who, upon post post-mortem inspection, were found to have suffered from something called chronic traumatic encephalopathy, or CTE.

From wiki..........

Chronic traumatic encephalopathy (CTE) is a progressive degenerative disease found in people who have had a severe blow or repeated blows to the head. The disease was previously called dementia pugilistica (DP), i.e. "punch-drunk", as it was initially found in those with a history of boxing. CTE has been most commonly found in professional athletes participating in American football,rugby, ice hockey, boxing, professional wrestling, stunt performing, bull riding, rodeo, and other contact sports who have experienced repeated concussions or other brain trauma.

This hits slightly home with me, because one of the players who was diagnosed with CTE was a friend of mine.  Jovan Belcher.  The middle linebacker for the Chiefs, who was involved in a murder-suicide.  He killed his girlfriend at the time, then drove to the Chiefs facility where he shot himself.

Junior Seau, the all time great for the San Diego Chargers, shot himself in the chest, so that his brain could be examined.  

On January 10, 2013, Seau's family released the NIH's findings that his brain showed definitive signs of CTE. Russell Lonser of the NIH coordinated with three independent neuropathologists, giving them unidentified tissue from three brains including Seau's. The three experts along with two government researchers arrived at the same conclusion. The NIH said the findings on Seau were similar to autopsies of people "with exposure to repetitive head injuries."

Seau had no prior reported history of concussions.  Junior was a football warrior.  Anyone that ever watched him play knew the kind of wreckless abandon he played with and he was admired and feared as a tenacious player.  But in the end, his brain just couldn't take the damage that had been caused by all the human car wrecks he had subjected himself to.  

Neither Jovan or Junior are alone in this regard.  All it takes is a google search to find all of the players whom, upon autopsy, suffered from CTE.  

Sports related concussions occur when there is a sudden acceleration or deceleration or rotational forces imparted to the brain.  The connection between TBI and CTE is clear.  CTE is caused by those who have suffered repeated concussions or traumatic brain injuries, such as those in contact sports, and even our military personnel.  

http://www.protectthebrain.org/Brain-Injury-Research/What-is-CTE-.aspx

The brain of an individual who suffers from chronic traumatic encephalopathy gradually deteriorates and will over time end up losing mass. Certain areas of the brain are particularly liable to atrophy, though other areas are prone to becoming enlarged.

The symptoms of CTE can be debilitating and may have life-changing effects for both the individual and for his or her family. Some of the most common include loss of memory, difficulty controlling impulsive or erratic behavior, impaired judgment, behavioral disturbances including aggression and depression, difficult with balance, and a gradual onset of dementia. An individual with CTE may mistakenly ascribe the symptoms to the normal process of aging, or might receive a wrong diagnosis due to the fact that many of the symptoms are similar to other conditions such as Alzheimer's or Parkinson's disease. CTE has been diagnosed in several notable cases which received widespread media attention, including the suicide deaths of NFL player Junior Seau, and professional wrestler Chris Benoit who committed suicide after murdering his wife and son.

Obviously,  this is a very disheartening thing to read.  And it's one of the reasons I detest when people start talking about how "watered down" the NFL has become because they don't allow people to "spear" people anymore, or lead with their head in tackling.  I mean, I played ball.  At no one was I ever taught to lead with my head in tackling drills.  The guy sitting on the couch drinking his Coors Light on Sunday afternoon complaining about how "pussy" the league has become, will never ever sit in a trainers room after the game wondering what his name is, where he is, or deal with the incredible migraines that come in the post concussive state.  

With all that said, one of the things I happened across when I became involved in using exogenous ketones was the fact that the brain uses ketones in a very preferable way for fuel.  

So what's the tie in here, you ask? 

During a TBI, glucose metabolism is depressed.  

Mild traumatic brain injury results in depressed cerebral glucose uptake: An (18)FDG PET study.

http://www.ncbi.nlm.nih.gov/pubmed/23829400

Moderate to severe traumatic brain injury (TBI) in humans and rats induces measurable metabolic changes, including a sustained depression in cerebral glucose uptake. However, the effect of a mild TBI on brain glucose uptake is unclear, particularly in rodent models. This study aimed to determine the glucose uptake pattern in the brain after a mild lateral fluid percussion (LFP) TBI. Briefly, adult male rats were subjected to a mild LFP and positron emission tomography (PET) imaging with (18)F-fluorodeoxyglucose ((18)FDG), which was performed prior to injury and at 3 and 24 h and 5, 9, and 16 days post-injury. Locomotor function was assessed prior to injury and at 1, 3, 7, 14, and 21 days after injury using modified beam walk tasks to confirm injury severity. Histology was performed at either 10 or 21 days post-injury. Analysis of function revealed a transient impairment in locomotor ability, which corresponds to a mild TBI. Using reference region normalization, PET imaging revealed that mild LFP-induced TBI depresses glucose uptake in both the ipsilateral and contralateral hemispheres in comparison with sham-injured and naïve controls from 3 h to 5 days post-injury. Further, areas of depressed glucose uptake were associated with regions of glial activation and axonal damage, but no measurable change in neuronal loss or gross tissue damage was observed. In conclusion, we show that mild TBI, which is characterized by transient impairments in function, axonal damage, and glial activation, results in an observable depression in overall brain glucose uptake using (18)FDG-PET.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2652873/

In contrast to dietary approaches to re-establish TBI-induced deficiencies in brain metabolites, diets have also been used to replace or redirect essential brain substrates. TBI-induced impairments of the glucose metabolic machinery may make glucose a less favorable energy substrate. In fact, hyperglycemia has been long associated with poor outcome after TBI. Early administration of glucose after severe TBI suppresses ketogenesis, increases insulin and increases lactic acid production (Robertson et al., 1991). TBI patients who were fasted or maintained on a ketogenic-like diet to minimize hyperglycemia showed significantly lower plasma glucose and lactate concentrations, elevated ß-hydroxybutyrate levels and better urinary nitrogen balance compared to standard fed patients (Ritter et al., 1996). Similar plasma substrate changes were observed with 24-hr starvation in the adult rodent after controlled cortical impact injury. The fasted animals showed significant cortical tissue preservation, improved cognitive outcome and improved mitochondria bioenergetics (Davis et al., 2008).

As I've had to read through all of these very, very scientific/medical studies, what I learned was that post TBI there is an immediate but transient elevation in cerebral glucose metabolism, followed by a prolonged period of glucose metabolic depression. The brain is metabolically flexible. So it has to ability to tab into various fuels for different needs.

For example, during fasting (not starvation, but fasting!) two thirds of the brain fuel is derived from ketones. The rest come from lactate, pyruvate, amino-acids, glycerol and other gluconeogenic precursors.

Post TBI, we have seen in studies on rats (and humans) that there is a tremendous demand for energy to restore homeostasis. To repeat myself, there is a depression in glucose metabolism during this period. Meaning, the brain cannot use glucose as needed in order to meet the demands required for said repair. This is something seen in studies over and over again.  

So where does it try to derive fuel from? 

Apparently, lactate and ketones.

TBI-induced impairments of the glucose metabolic machinery may make glucose a less favorable energy substrate.

But what I found interesting, is that the brain had no problem using ketones and lactate as the fuel sources to help return it to homeostasis, and that the ketones also had neuroprotective effects after a TBI had occured.


Whether ketosis is achieved by starvation or administration of a ketogenic diet, the common underlying conditions of low plasma glucose in the presence of an alternative substrate (ketones) have consistently shown neuroprotective effects after various types of brain injury.

Allow me to lead you down a rabbit hole for just a second, but I promise I'll round you back to the main point in all of this eventually.  

http://www.ncbi.nlm.nih.gov/pubmed/23228828

A dietary therapy for pediatric epilepsy known as the ketogenic diet has seen a revival in its clinical use during the past decade. Although the underlying mechanism of the diet remains unknown, modern scientific approaches, such as the genetic disruption of glucose metabolism, are allowing for more detailed questions to be addressed. Recent work indicates that several mechanisms may exist for the ketogenic diet, including disruption of glutamatergic synaptic transmission, inhibition of glycolysis, and activation of ATP-sensitive potassium channels. Here, we describe on-going work in these areas that is providing a better understanding of metabolic influences on brain excitability and epilepsy.

I bolded that part for a reason.  Because it is related to the cascading issues that come with brain injuries.  

Glycolysis and TBI - 

The postinjury period of glucose metabolic depression is accompanied by adenosine triphosphate decreases, increased flux of glucose through the pentose phosphate pathway, free radical production, activation of poly-ADP ribose polymerase via DNA damage, and inhibition of glyceraldehyde dehydrogenase (a key glycolytic enzyme) via depletion of the cytosolic NAD pool. Under these post-brain injury conditions of impaired glycolytic metabolism, glucose becomes a less favorable energy substrate. Ketone bodies are the only known natural alternative substrate to glucose for cerebral energy metabolism. While it has been demonstrated that other fuels (pyruvate, lactate, and acetyl-L-carnitine) can be metabolized by the brain, ketones are the only endogenous fuel that can contribute significantly to cerebral metabolism.

ATP and TBI - 

http://dmm.biologists.org/content/6/6/1307

Glucose is the primary fuel source of the adult brain and its processing through the glycolytic pathway provides carbons for the tricarboxylic acid (TCA) cycle for energy production in the form of ATP. 

Comparison of glucose metabolic changes in TBI between different age groups within the pediatric population, or a comparison between adults and children, has not yet been made in humans. Regardless of age, the prolonged glucose metabolic depression reflects a period of time during which glucose uptake into the brain is compromised. This could cause downstream negative effects if the energy demands of the brain are not sufficiently met.

Pyruvate dehydrogenase (PDH) is the enzyme that connects the glycolytic pathway to the mitochondrial TCA cycle. Phosphorylation of the E1 subunit of PDH, which inhibits PDH function and therefore carbon entry into the mitochondria, has been shown to occur at a higher frequency than normal at 24 hours after CCI injury (Xing et al., 2009). These TBI-induced alterations in glycolytic enzyme functioning ultimately decrease the ability of glucose to be efficiently processed for oxidative metabolism, and thereby contribute to the post-TBI energy crisis, reflected by reductions in ATP production (see poster, panel D).

Free radicals and inflammation - 

The other issue involving TBI is the increase in both inflammation, and free radicals.  

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1276814/

In addition to increasing ATP production while reducing oxygen consumption, ketone body metabolism can also reduce production of damaging free radicals [14,16,48]. The semiquinone of Q, the half reduced form, spontaneously reacts with oxygen and is the major source of mitochondrial free radical generation [14,51]. Oxidation of the Q couple reduces the amount of the semiquinone form thus decreasing superoxide production [14]. Since the cytosolic free NADP+/NADPH concentration couple is in near equilibrium with the glutathione couple, ketone body metabolism will increase the reduced form of glutathione thus facilitating destruction of hydrogen peroxide [14]. The reduction of free radicals through ketone body metabolism will also reduce tissue inflammation provoked by reactive oxygen species. Thus, ketone bodies are not only a more efficient metabolic fuel than glucose, but also possess anti-inflammatory potential.

Ok so where am I going with all of this?

First off, despite the fact that death via TBI is a major issue in this country, and a major issue in contact sports, believe it or not it's not at the forefront of research in regards to finding the most effective therapeutic solutions for it.  

What we have, for the most part, is a lot of research done on rats, and some research done on humans.  This is quite puzzling to me because TBI is, once again, a major cause of death in the world.  

But even if someone doesn't die, the amount of damage done after repeated bouts of TBI like in Rugby, boxing, football, hockey, etc means that those athletes tend to live an exceptionally poor quality of life after sports. With many, such as Jovan and Seau actually resorting to suicide.  

I'm not saying that exogenous ketones will fix all the problems associated with TBIs.  But if you look at the fact that they reduce free radicals, reduce inflammation, and provide the brain with a more preferred fuel source while glucose metabolism is depressed, then I can't understand for the life of me why more people who are responsible for the health and well being of our pro athletes aren't at least including exogenous ketones as part of dietary therapy for their players who have or do suffer from brain injuries.  

What we're currently doing is not working.  And when you add up what evidence we do have, I do see promise in regards to the inclusion of exogenous ketones as part of therapy to help players suffer minimal damage in the post TBI stages.  

Or they can just keep feeding them prescription pills from big pharma.  That's clearly working.  /sarcasm.

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The modalities of training efficiently

Specific goal prioritization - Decide on one thing

Wanting to squat more weight and wanting bigger quads are not the same goal.  Squatting more weight might not even be an efficient means to that end.  And yet so many guys that say they are interested in growing get caught up in the trap that if they aren't hitting PR's at every training session, that they weren't stimulating growth, or getting better.

Strength and hypertrophy are more like, distant cousins than identical twins.  Basically there are some connective ideologies but there's also a lot of things that make them very dissimilar.  I mean ping pong is called table tennis but I doubt Serena Williams is going to challenge any Olympic level ping pong players.

Training for maximal strength in order to grow is a lot like trying to get better at tennis in order to be better at ping pong.  Yeah, you might find some carryover but for the most part you're not maximizing what is most effective.

A good example of this would be someone who say, does distance running.  They might throw in some track work intervals once a week or twice a month, but the majority of their training is built around doing the things needed to get better at distance running.  That's because whatever it is you are trying to maximize with training has to be geared towards maximal responses.

Strength training has a large neurological base associated with it.  Training for size, does not.

One can actually train with relatively low intensities (as little as 30% of 1RM) and stimulate growth via muscle protein synthesis.  But you cannot develop maximal strength at loads that low.

There's at least a dozen other things I could write out that separate training for strength vs size, from training frequency, to volume, to how the movements are even executed, but without doing that I am just going to say that your training should always be focused on a singular goal to achieve as quickly and as efficiently as possible.

If you are training for strength, training for strength.  Do not plan on getting "ripped" at this time.  There might be some growth as a side effect, but again it absolutely will not be maximized because training for maximal strength is not training for maximal growth.  Generally this means training in low to moderate rep ranges using intensities between (give or take) 75-90%.  Volume can be waved throughout periodized blocks all depending on where the intensity zone is being utilized at the present time.  Training should be centered around being explosive, refining technique and motor patterns and not generating fatigue through training to failure.

If you are in a fat loss stage, then muscle retention is a priority.  That means you must give your body a reason to hold on to the amount of lean tissue it is currently in possession of, while using your diet and probably some form of conditioning to put yourself into a hypocaloric state.  This means you should still train hard, but understand two things - neither increased mass (you cannot get big and ripped at the same time) nor increased strength should be counted on at this time.

If  you are training for maximal growth, then (obviously) you will have to have an excess of calories coming in to support the growth process.  Training should reflect the fact that you are training for maximal growth via efficient training modalities like increased time under tension.  Emphasis should be placed on putting the muscles into fully lengthened and shortened positions (through various movement selection) and generating as much tension as possible on the muscles you are trying to work.  Generally speaking this also means rep ranges of 8-20 or possibly even more.  Generating fatigue in some fashion (where failure is hit, or something close to failure is achieved) is also highly desired as well.

As you can see, whatever phase you feel like you need to concentrate on, they have very different approaches in order to maximize efficiency.  Of course, none of these are completely set in stone or are "rock hard facts" but through both anecdotal evidence and what we've seen through research these are solid starting guidelines for most.



Cognizant selection - Know why you are doing what you are doing

A training program or methodology is generally made  up of a myriad of properties.  And you should be able to answer the questions under each one without hesitation.

Training volume.

Why are you using X amount of sets?

Training frequency.

Why are you training Y number of times per week?

Training intensity (both perceived effort and percentage of 1 rep max).

Why are you using certain loading in  your training or training with a certain RPE?

Movement selection.

Why are you performing each movement in the manner that you are?

Rep range (which could also fall under the volume umbrella).

Why are you using certain rep ranges for both warm ups, and working sets?

Movement execution.

Why are you performing each movement in the manner that you are?

For every single part of your training, you should have a clear understanding of what you are doing what you are doing.  Why you are training X number of days per week, why you are doing your chosen rep range, why you are using Y amount of volume, and why you are using certain training intensities.

All of these variables should be defined by you for very specific reasons.  Even to the point of having variation within training sessions built on how you feel for the day.  For example, if you got very little sleep or nutrition was sub par for the day (or the day before) or you're just generally feeling very under the weather, then "going for it" on such a day is probably not a good idea.

Being aware of your own natural recovery rhythms is a huge factor in sustaining progress.  Getting injured because you refused to deviate from a plan that called for you to do a max set of 10 reps on bench press, when you could "feel" things were off that day, means you refused to leave your training ego at the door.

This too means you know why you are pulling back on training intensity for the day.  So you backed off because you knew you your body was not going to be capable of putting forth a significant amount of effort.  This is not an excuse to be lazy.  It simply means that you're aware that the nitro button shouldn't be pushing during a time when the engine was sounding clunky.

This is where so many people lose out on months, years, potentially a decade or more of productive training.  Because they often just copy what someone else is doing without ever questioning why they themselves are doing it and/or never learn what would be best for them.  Copying what someone else is doing means  you've decided to put your logical reasoning to the side and just be a training zombie.
I'm not saying you can't borrow something from someone else that does in fact work well for you, but using wholesale routines "because that big dude trains that way" doesn't make a lot of sense.  You're not that big dude.  And he probably didn't become that big dude training the way he does now.

One of the most important aspects of creating an efficient training program or ideology that paves a faster way to goal actualization is to breakdown every facet of what you're doing, and identify the reasoning for it.

If you cannot answer the questions provided, then take some time to think about it until you can.  Then start to apply the answers in your own training, and see what it produces.


Individual bias - What resonates with you

Perhaps the single most important factor in regards to training efficiently, or shall we say, maximizing results, is to embrace what resonates with you.

Some people will find that some sort of DUP or block methodology will really appeal to them.  And some won't.  Some people will love training lower volume with brutal all out intensity techniques.  And some will prefer a much higher degree of volume in their training, avoiding failure all together.

Despite all the studies you will ever read, the one thing none of them can take into account is what resonates with each individual.  In regards to pretty much everything.  That's life, and training.

Some people like cats.  Some people like dogs.  Some like both.  Some don't like either.

If you asked each person their reasoning for such, you'd likely get some simple answers as to why, but believe it or not, most of those things are just surface level responses and the majority of people cannot really tell you the deep meaning of why they gravitate towards certain things in life.  They know they do, and they have their own answers, but they cannot explain to you why they like "red headed women".

"Because I'm attracted to them."

Yes, that's a really surface level answer, but truthfully people can't really tell you the why behind their answers.  And let's be clear, with everything in life you don't have to.  The person who loves country music, and hates metal can't tell you why they do.  They just do.  And vice versa.  Again, one person may say "it's all a bunch of screaming I can't understand" or the metal guy may say "country sucks because it's a bunch of whining."

Again, surface level answers.

People can't really answer the "why" to those answers.

"Why don't you like all that screaming in metal music?"

"Because I don't."

To them, that's enough.  And it is.  No one has to justify their reasoning for their preferences.  But there tends to be reasons deeper than "I do/don't like..." certain things.  But I'm not a psychologist and I don't intend to ask  you about your relationship with your mom/dad or your childhood fears.

Training is no different.  People are going to gravitate towards certain training "styles" because it speaks to them and they enjoy it.  There's probably a deeper reason "why" to all of that, but I can't answer those things for every person.  Some people are more analytical in their approach to things, and like structure.  Some people gravitate towards a more haphazard brutality style approach and tend to often live their life with a bit more edge to it as well.

That's just my own observations and is in no way factual.  I'm just never surprised when I have a chance to get to know someone personally, what training style they tend to favor.  It's almost always a reflection of the actual person I know.

But here's the thing.  You will be the most consistent with whatever training program resonates with you the most.  Even if the training program is sub-par in some aspects, if you're applying it will consistency and exceptional effort, then results will manifest themselves in some way.

Dieting is no different.  People have been debating low fat/low carb for fat loss for decades now and there have been a zillion studies done with each side trying to prove one is more effective than the other.  When the fact is, the most effective one, is the one someone can use on a consistent basis because they enjoy it (I mean to whatever degree you can REALLY enjoy dieting).  From satiation to food selection, people will be more likely to stick to the diet that for whatever surface level reasons, resonate with them.


Conclusion - 

These three things are basically the pyramid or trinity or trifecta in regards to outlining a complete training/diet strategy to reach your goals the fastest.  Within each of these there is of course, a complicated set of questions and answers that you must ask, and be willing to answer.  Once  you can effectively "fill in the blanks" to all of that, you'll be well on your way to smashing through roadblocks and understanding how to apply the things that best suit you and your individual needs.

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