The Longevity & Brain Benefits of Vigorous Exercise | Dr. Rhonda Patrick

welcome to the F my fitness podcast I'm your host Rhonda Patrick today we're diving deep into the science and practicality of incorporating vigorous intensity exercise into our lives it's not just about living longer it's about enriching the quality of life at essentially every stage and also influencing brain function during vigorous exercise our muscles essentially become mini biochemical Labs synthesizing compounds like lactate and myocin these aren't just muscle bound they get into circulation travel to far off tissues and they signal to them and they have a variety of benefits including the synthesis of elements like brain

dve neurotrophic factor or bdnf crucial for brain health and neuronal health they also potentially initiate anti-cancer mechanisms not only are muscles little chemical producing factories but they also act like sponges to soak up compounds that can be harmful to the brain improving mental health and reducing neurodegenerative disease risk we're going to dive deep into the realm of V V2 Max optimization V2 Max is not just about a measure of cardiorespiratory Fitness it's directly linked to longevity essentially the higher your V2 Max the longer you're likely to live and there doesn't seem to be an upper

limit to the life extending benefits of enhanced cardiorespiratory Fitness at least within your genetic potential we'll get into the details of how to calibrate high-intensity efforts with Zone 2 training methodologies for improving BO2 Max with the spotlight on the Norwegian for by4 protocol and even touch on some straightforward tactics like assessing BO2 Max so the pragmatic test which is the 12-minute run test equally important we'll navigate through the processes of mitophagy and mitochondrial biogenesis these are cornerstones for cellular Rejuvenation essentially reversing the aging process on a cellular level there's a lot of questions to answer

what is vigorous exercise what is high-intensity exercise what about Zone 2 training so let's start by covering what is is not vigorous exercise Zone 2 training is also sometimes known as aerobic Based training it primarily targets aerobic Energy Systems and can be sustained for longer durations we're talking an hour and more some experts Define this type of training to be around 70 to 80% of maximum heart rate um possibly lower for people that are unfit um it's also defined by the talk test so you should be able to talk Comfort comfortably but not sing so

you should be a little breathy when you're talking but still able to talk comfortably zone two training involves exercising at a moderate intensity it's a steady state type of lactate threshold training lactate threshold refers to the point at which the body begins to produce lactate at a faster rate then it can clear it away so keep in mind there's a lot of individual variation in determining the lactate threshold because people can have different Baseline lactate levels for one which is typically around 0.9 to to 1 millimolar generally speaking um people also have different rates of

lactate production and clearance and even at the same relative exercise intensity so for example trained athletes might have a higher lactate threshold in terms of both exercise intensity and lactate concentration compared to untrained individuals genetics also play a role there are many great podcasts out there covering Zone 2 training um including Peter AAS the drive with guest Dr Dr enigo sanon now let's talk about vigorous exercise so generally speaking vigorous exercise represents a level of exertion where exercise goes beyond the lactate threshold which means lactate begins to accumulate in the muscles more rapidly there are

various intensities within vigorous exercise so level intensity referred to as the maximal steady state threshold sometimes called Zone 3 is above the lactate thr threshold and it's challenging to hold a conversation and it's difficult to maintain this level of exercise for longer than 20 to 30 minutes this level of intensity is somewhere between 80 to 85% max heart rate however vigorous exercise also includes exercising at intensities higher than this so a higher intensity training where there's significant amount of lactate accumulation and you're close to your what's called anerobic threshold this is a level of intensity

usually around 85 to 95% max heart rate and it's difficult to maintain for longer than a few minutes sometimes this type of training intensity is called zone four training then there's the All Out near maximal intensity and this is sometimes called zone five Training these are shorter intervals and it's generally hard to maintain this level level of intensity for um longer than 1 minute so when we're talking about high-intensity interval training it involves alternating between periods of high-intensity vigorous exercise and periods of lower intensity rest depending on the the high intensity interval training or hit

for short protocol these can include intervals ranging from zone three to zone five followed by recovery periods the idea that high-intensity interval training is only Anor robic is a misconception while high-intensity interval training exercise does rely more heavily on Anor robic Energy Systems it still required significant aerobic metabolism so hit can improve both aerobic and anerobic fitness and it's my opinion that getting your heart rate to at least 80% max heart rate so that that being at least 80 uh percent is a really good place to be if you are targeting brain benefits and we'll

dive a lot into that in a minute but I want to start by talking about cardiorespiratory fitness health span and Longevity so V2 Max is a measure of maximal oxygen uptake which reflects an individual's ability to utilize oxygen during exercise it's considered one of the best indicators of cardiorespiratory Fitness and it's associated with improved healthspan increased lifespan higher cardiorespiratory levels as measured by V2 Max have been consistently leaked to A reduced risk of mortality and longer lifespan so in the podcast when I use the term V2 Max just keep in mind that it's a measurement

of cardiorespiratory Fitness the greatest longevity benefit that comes from improving your V2 Max is from people starting from a below average V2 Max and moving anywhere above average so even going from a below normal V2 Max for your age group and gender to a low normal is associated with a 2.1y year increase in life expectancy bumping that up going from a below below normal to high normal V 2 max is associated with a 2.9 year increase in life expectancy and going even further to the upper limit of normal is associated with 4.9 years so almost

5year increase in life expectancy on average each unit increase in bi2 Max so that's 1 milliliter per kilogram per minute is associated with a 45 day increase in life expectancy in another study involving only men for every 10 unit increase in V2 Max so this would be then 10 ms per kilogram per minute there was a 70 177% lower risk of death from cancer and a 11% lower all cause mortality so dying from many different um Co non-accidental causes of uh death another study published in Jama in 2018 found that there was no apparent upper

limit to the benefit of cardiorespiratory Fitness on mortality within normal ranges of human life expectancy of course um in fact the study reported that Elite performers these are people that performed in the top 2.3% on the fitness test had an 80% reduction in mortality risk compared to the lowest performers so they performed in the bottom 25% on the fitness test and if you compare the elite performers to the high performers so these folks did really well but they were just under the elite they were they were between the top 25% and the top 2.3% the

elite performers had a 20% mortality risk decline compared to even those High performers but going back to what I said earlier about just moving out of that low fitness group will give huge advantages to on life expectancy so people in the low fitness group had a fivefold higher risk of death than the elite performers but what is also so interesting is that the risk of dying due to low Fitness was similar or even B bigger than risks associated with having heart disease smoking or diabetes so being fitter is really good for your health at every

level of fitness and there's always room for improvement so the question is well how can we improve our BO2 Max um lots of different training protocols Zone 2 training for example high-intensity interval training you know vigorous intensity exercise all improve cardiorespiratory Fitness and can increase V2 Max um hit has been shown to significantly improve E2 Max even with shorter training durations this is because hit recruits both aerobic and Anor robic Energy Systems and increases the intensity of the workout resulting in um greater greater cardiovascular stress and then adaptations um but this is important there are

individuals who engage in more moderate intensity you know steady state zone 2 training that do not experience significant improvements in V2 Max in fact research has shown that approximately 40% of people do not see a measurable increase in their V2 Max even after engaging in guideline-based moderate intensity exercise which is about 2.5 hours of uh of this type of exercise per week for several months but when these what are called non-responders Incorporated more vigorous intensity exercise such as high-intensity interval training they do start to see improvements in V2 Max so this suggests that adding higher

intensity exercise to an exercise routine can help eliminate that non-response and also can lead to Greater benefits in cardiorespiratory Fitness the reason for non-response um to moderate intensity exercise it's not completely understood but um the addition of vigorous intensity exercise is important for overall improvements in BO2 Max and engaging in more vigorous exercise seems to Prov provide a stronger stimulus for physiological adaptations that lead to increased cardiorespiratory Fitness so again I think these findings do really sort of highlight the importance of incorporating vigorous intensity exercise particularly incorporating maybe uh high intensity interval training into a

training routine and obviously for individuals who are time pressed and can't dedicate several hours per week to doing a more type zone two type of training including shorter sessions of higher intensity exercise can still have significant improvements in BO2 Max and overall health uh so you might be wondering you know how much time do I dedicate to my more vigorous type of exercise versus a more moderate intensity Zone 2 type of training and I really think that answer depends on a lot of factors your individual goals um what you enjoy doing most what you're going

to do the most I mean all those things are important because at the end of the day uh establishing a habit having an exercise routine that you're going to consistently do is what is most important uh for endurance athletes I mean the answer is easy right you're already dedicating several hours a week to doing more zone two training and about 20% of that training is dedicated to to Shorter higher intensity workouts more vigorous intensity workouts and this is commonly known as the 8020 rule but um remember this is this is people that are doing extensive

amounts of training anywhere between 10 to 30 hours a week week um it's I think it's a common misconception to apply that 020 rule to like any committed exerciser and any casual exerciser who are doing well under less than 10 hours a week as you think about um someone who is a committed exerciser maybe you work out 3 to 5 days a week how much of that time should be spent doing vigorous intensity exercise I would say for VO2 max and other adaptations we're going to discuss including the brain um about half of that exercise

training time I think should be spent in vigorous doing a vigorous exercise so again you want to be uh 80 at least 80% of your max heart rate or or more uh obviously there's resistance training to to incorporate as well into any training program um there's casual exercisers so people that work out maybe two to three times a week uh they should probably spend more than half of their time doing more vigorous intensity exercise I think this this ensures you're pushing your limits and you know making sure that you're getting adaptations Fitness gains in a

shorter period of time there are a variety of V2 Max training protocols so for people that are looking for that more vigorous exercise using you know using high-intensity enal training to improve their V2 Max um the key here is longer intervals so incorporating longer intervals such as 2 three four maybe even five minutes at the highest workload you can sustain for that time and then performing four intervals with rest and Recovery in between um each of those so this protocol may require maybe a 20 minute time commitment but it can lead to significant improvements in

V2 Max there's a few examples of a V2 Max training um Dr Martin gabala who was a recent podcast guest gave a variety of of examples of this so there's 3 to five minute repeats at the highest sustainable intensity we talked about doing um those 3 to 5 minute intervals that you can maintain and then you rest and recover and repeat those intervals uh for for a total of 20 minutes I think a a popular variation of this is called the Norwegian 4x4 interval training protocol so the intervals are 4 minutes long and you're aiming

for about 85 to 95% of your max heart rate or the maximum level of intensity you can maintain for the entire four minutes um these interval these intervals can be brutal so the recovery period is 3 minutes long and the intensity is significantly lower like light light exercise more like a Zone one training exercise you want to allow yourself recovery time the clearance of lactate you want your heart rate to come down significantly so that you can prepare for the next 4minute interval so these four minute intervals are repeated um four times and again in

between each interval is a 3 minute recovery so that's the the nuran 4x4 interval training um there's another type of BO2 Max training protocol it's the one minute on one minute off protocol this is where you perform one minute of intervals at the highest intensity you can do for 1 minute and then it's followed by a one minute recovery period and then you repeat this interval pattern 10 um or maybe five times for about 25 minutes or so and and this protocol also is effective at improving BO2 Max and it does provide a lot of

flexibility in terms of time commitment um it it's also not as uh you know grueling in terms of like doing a 4-minute interval versus a one minute interval one minute intervals are a little bit um you know less intense and and less painful obviously it's important that you know these Protocols are sort of templates they vary a lot based on individual fitness goals um you know there's other protocols out there that can improve V2 Max the key is like a longer interval longer than like a Tabata like a 20 second interval and so you know

probably about at least 1 minute at the highest sustainable intensity that you can do I think the Norwegian 4x4 protocols probably one of the best out there um one of the best hit protocols out there for improving V2 Max so how do you measure V2 Max um without equipment found in an exercise physiology uh physi ology lab um it's obviously challenging there's several sort of tests that have been developed and verified for getting an an an estimate of your V2 Max so they don't directly measure maximum oxygen uptake but they predict your V2 Max based

on the relationship between your exercise intensity and your oxygen consumption um they're sort of useful in determining whether or not you're improving V2 max if you're testing a a type of training protocol so the there's a couple of really like I said validated tests that have been validated in scientific literature um that can that can sort of be done probably one of the best ones is the 12 minute run or sometimes called walk test depending on your level of Fitness um it's often also referred to as the Cooper test and um it involves having the

participant run or jog as far as possible in 12 minutes so you're supposed to paste yourself evenly you don't want to start too fast and the test should be conducted on a flat surface so like a track field is the best you don't want to have Hills and stuff because it's it's about you know the the maximum amount of distance you can cover in 12 minutes and if you have Hills and stuff that's going to less that it's going to be more challenging and um you know the distance won't be quite as far so uh

you'll need a fitness device something that Rec can record your your distance an Apple Watch or you know Fitbit or something and depending on your Fitness level you can walk or you can run um or a combination so the distance covered within that 12-minute period serves as the primary metric for evaluating BO2 Max which is then estimated using a formula so it's its distance in meters minus 54.9 and then divided by 44.7 3 and you can look this formula up just look up the Cooper test to find the formulas um online again um you know

there's there's some other validated test but I think that's probably the one of the best better ones out there you'll need a device like an Apple Watch uh or some some sort of other device that can measure your distance but there's also the some of these devices and wearables do estimate V2 Max during exercise using heart rate and your motion data um you know for best results you have to make sure all your personal information's in there like your age and your weight and gender you know all that stuff but that's another you know possibility

I would say the 12-minute run or walk test is a more it's a better way to do it particularly if you're trying to do something like the 4x4 nor Norwegian um hit protocol to to measure V2 Max improvements you want to see if what you're doing is improving your your estimated V2 Max so I think that the 12-minute run test is a is a good way to do that I want to sort of change gears for a minute and talk about um you know something that I also think is pivotal and it's it's a unique

role for vigorous exercise in playing a role in enhancing Health span and it has to do with changes in heart structure so as we age the heart undergo specific inevitable changes right related to the a aging process so it tends to get smaller uh it gets stiffer and this can impact the heart's efficiency uh potentially reducing our Exercise capacity elevating our risk for cardiac issues um but there can be exercise intervention like consistent aerobic exercise with a high proportion of it being vigorous intensity that can actually combat some of these effects so there was a

landmark study published from Ben lavine's group and it was an intervention study and it showed that two years of vigorous exercise in 50y olds was able to reverse the aging of their hearts by as much as 20 years effectively making their hearts look more like a 30-year-old which in my opinion is simply astonishing you're taking a 50-year-old heart and making it look like a 30-year-old heart now the exercise protocol used in this this particular study uh it was a protocol that that gradually increased the exercise intensity and also frequency so again I mentioned it was

a two-year intervention by the end of six the first six months participants were exercising about five to six hours a week with a large portion of training being in that maximal steady state um intensity exercise like which I referred to earlier in the podcast it's it's often sometimes called Zone 3 it is a type of vigorous intensity exercise um they also were incorporating more High higher intensity exercise so they also did the Norwegian 4x4 V2 training V2 Max training protocol I just referred to and they did that once a week and um I just think

it's like I said it's simply astonishing that you know you take these 50 year olds and after 2 years of a more vigorous intensity exercise um training protocol it essentially reversed the effects of Aging in the heart okay so let's shift gears yet again and talk a little bit about metabolic adaptations and again this is where I think vigorous exercise really shines um particularly high-intensity interval training it improves glucose control insulin sensitivity um more more efficiently and more potently than even continuous you know moderate intensity workouts and uh you know I do think that of

course both exercise type you know training protocols can enhance muscle adaptations and glucose regulation um hit really seems to to do it quicker and um again more robustly whereas moderate intensity exercise kind of Demands longer sessions for comparable outcomes so research has found that high-intensity inal training can enhance the muscle ability to take up glucose and improve glucose transport capacity so during high-intensity interal training and during vigorous exercise there's a a a demand a rapid you know a demand for Rapid energy production and so the body relies both on aerobic so oxygen using and anerobic

non oxygen using metabolic pathways to generate this energy the anerobic pathway can lead to the production of lactate especially when the intensity of exercise surpasses the point at which the oxygen intake can keep up with the energy demand um and and so this is sometimes often referred to as the lactate threshold as we talked about for a long time lactate was considered primarily as a waste product contributing to muscle fatigue and uh you know this has of course been completely revers Recent research Arch has you know totally changed this understanding um lactate generated in muscle

tissue is transported not only back into muscle and into mitochondria to be used as an energy source but it also when it starts to accumulate at higher levels travels systemically into circulation and gets transported to other tissues like the heart the liver the brain where it's used for energy um it's also used as a signaling molecule so this is known as the lactate shuttle and was pioneered by Dr George Brooks who has really changed the field and um he also happened to be my second podcast guest ever on on this podcast um anyways lactate you

know it it it I mentioned it acts as a signaling molecule in those tissues as well and you can think of a signaling molecule as a chemical messenger that is sending a message to other cells one of those messages is the upregulation of gluc glucose transport capacity so so vigorous intensity exercise high intensity interval training when when that lactate production accumulates it stimulates the expression and activity of glucose Transporters known on the muscle known as glute 4 and this is on the muscle cell membrane and so that lactate acts as a signaling molecule to increase

the transport of glucose Transporters on on the muscle cells and this then allows for more efficient uptake of glucose into the um from the bloodstream into the muscle even at rest and so consequently then insulin sensitivity is also improved and blood glucose levels are better regulated there's been several studies that have demonstrated that hit can improve glucose uptake enhance insulin sensitivity and decrease the risk of developing type 2 diabetes this may be due to the intense metabolic stress created during hit which leads to Greater activation of glucose transport great glucose Transporters um and improv glucose

clearance um so as I mentioned both high-intensity Neal training continuous moderate intensity exercise can also be effective at improving glucose transport capacity in the muscles um hit promotes rapid increases in glucose Transporters allowing for that efficient glucose uptake and utilization whereas continuous moderate intensity exercise although it's less intense still does also enhance gluc transport capacity um it improves the overall Fitness of muscles as well so you know again it's just a longer duration of exercise time to to get there and um with the with the lactate generation that happens with you know high-intensity high-intensity exercise

you're getting that immediate signal from lactate to increase the gluc glute for Transporters and so it's a it's a very rapid and robust adaptation that happens there's other metabolic ad adaptation so um just just kind of talking about mitochondria mitochondria are very important and they play a lot of roles in the body but one of the most important ones is the production of energy in the form of ATP this is obviously very important for muscles but also hugely important for the brain um the heart the liver pretty much every organ athletes are very interested in

mitochondrial health because they want their muscles to efficiently and effectively produce energy when they're training but mitochondria are also very important in the context of Aging as we age our mitochondria become less efficient at producing energy and this poses a problem for physical activity but also just for normal functioning of our organs now that problem of mitochondria not producing enough energy can actually be overcome by increasing the mitochondrial volume or what's called mitochondrial biogenesis an exercise particularly vigorous exercise is one of the best ways to do that so one of the most powerful indicators of

healthy mitochondria is the ability to generate new healthy young mitochondria called mitochondrial biogenesis vigorous intensity exercise like high-intensity high-intensity interval training I mentioned um it's one of the most powerful stimulators of mitochondrial biogenesis this has to do with the metabolic stress that is induced from vigorous inity exercise the lactate itself again lactate is a signaling molecule when you're producing greater amounts of lactate that actually activates one of the major Pathways that regulates mitochondrial biogenesis it's called pgc1 Alpha and again lactates acting as a signal to produce more of that pgc1 Alpha so when we perform

vigorous intensity exercise such as hit that lactate generated from the muscles it's shuttled into the mitochondria because exercise increases the um the number of mitochondria per cell again mitochondrial biogenesis and the more lactate that's able then to be used as um energy or to produce energy and this is important to know if you're wanting to understand the bigger picture of where metabolism and and lactate utilization fit into you know Human Performance but it's also important to realize that athletes put around anywhere between like I said 10 20 30 hours of training in a week um

if they're endurance athletes and usually about 80% of that training is in you know the the the Moder intensity Zone to training world with the remaining 20% being vigorous intensity exercise like hit if they're if they're putting in 20 hours a week of of you know the of moderate intensity training then they're doing anywhere you know they're doing you know four anywhere between four to six hours a week of vigorous exercise like hit so just the portion of their vigorous exercise alone they are doing is more than what committed exercisers are doing so the question

is what's the best training protocol for a non-athlete someone that's perhaps a committed exerciser who is interested in Health and Longevity uh again both high-intensity interval training Zone 2 training also moderate intensity training can increase mitochondrial biogenesis in skeletal muscle hit does it more rapidly um it's a more potent stimulus again with with lactate being a signaling molecule um on the other hand zone two training you know for which is you know doing a more um moderate intensity exercise that's sustained for a longer duration does lead to an increase in mitochondrial content I think the

key here is the total volume of training so higher intensity higher intensity exercise is a smaller volume and it can result in more rapid larger increases in mitochondrial content while doing a more moderate intensity Zone 2 training also does the same thing um but it just requires larger exercise volume or duration your muscle's ability to use fat as a fuel is also closely tied to how many active mitochondria you have so in other words increasing mitochondrial content also determines the ability of muscles to be able to oxidize fat both high intensity anable training so vigorous

exercise and Zone 2 training increase the capacity for fat oxidation by increasing mitochondrial content Now by enhancing um the growth of new mitochondria you're increasing the activity of key enzymes involved in fat metabolism so one of those is the carnitine um palet transferase enzyme or the CPT enzyme both types of exercise training moderate and also vigorous intensity exercise do um increase the CPT enzyme capacity as well and you know obviously that is directly related to the utilization of fat as a fuel source so I think the bottom line here is that you know mitochondrial biogenesis

increasing mitochondrial volume is key for mitochondrial Health it's key for improving fat oxidation as well and both high-intensity interval training and a more moderate Zone 2 type of training will get you increases in mitochondrial volume so another way that exercise improves mitochondrial health is through a process known as mitophagy or mitophagy as some people call it so mitophagy is a type of autophagy which involves the selective removal of damaged or dysfunctional mitochondria from the cell or within the cell um this this process really helps maintain mitochondrial qual quality control and overall cellular health so when

you put stress on mitochondria through exercise the body triggers you know the elimination of damaged mitochondria and the replacement of those mitochondria with new healthy ones through mitochondrial biogenesis there's not a lot of direct human research on the effects of different training types of EX of of different training types of um different exercise training on mitophagy but I know of at least one human study that has found particularly vigorous intensity aerobic exercise enhances markers of mitophagy it's likely that both both vigorous exercise high-intensity interval training and more moderate exercise training can stimulate this process with

hit just getting you faster and you know the moderate intensity Zone to requiring a larger training B volume but overall you know both hit Zone 2 can promote skeletal muscle adaptations including mitochondrial biogenesis fat oxidation mitophagy this is a repeating theme of this podcast and also on the one that I did with Dr Martin gabala on high-intensity interval training I think the choice between the two really depends again on individual goals preferences the amount of time available for training and just what you love to do hit offers that time efficiency um it it potentially has

the the ability to have rapid improvements and adaptations in mitochondrial content while Moder intensity Zone 2 training can yield similar adaptations with a larger volume of Moder intensity exercise you know sustained for a longer duration but I do think that it's important to probably try to incorporate both types of exercise training for a more well-rounded way to kind of cover all your bases um and for those that are committed exercisers if you're putting in let's say anywhere between two to 5 hours of training a week it's it's my opinion that you know you you should

probably be doing a lot of a lot of that training or half of that training should be vigorous intensity exercise not only because the voax improvements we spoke about earlier but also because of brain benefits so let's talk about the brain exercise intensity like high-intensity interval training has been shown to have unique benefits for brain health um obviously all types of exercise are beneficial for the brain but high intensity exercise may have additional neuroprotective and cognitive benefits and one of the mechanisms that's thought to underly this is you know the the unique effects of you

know vigorous intensity exercise or hit on the brain because of the lactate production so during high-intensity exercise lactate is produced in large amounts as we've talked about about um largely as a byproduct of the metabolic stress you're you're kind of pushing that Anor robic threshold and when you produce lactate it's getting into circulation and it can cross the bloodb brain barrier there are lactate Transporters MCT Transporters on the bloodb brain barrier and it can you know cross the blood brain barrier and get into the brain where it then acts as a signal and it triggers

a variety of beneficial adaptations so um let's talk about some of the first you know lactate can be used by neurons as a preferential energy source so it's it's actually energetically favorable it takes less energy for mitochondria to to mitochondria to use lactate versus glucose so um in fact neurons are are used to using lactate because asites in the brain which are a supporting cell for neurons they're mostly glycolytic that means they're mostly using glucose as energy they're not using mitochondria and they're producing lactate as a byproduct so asites are turning out tons of lactate

in the brain and that lactate is be being taken up you know by neurons through the the MCT Transporters and used as energy so um there's actually even been studies showing that the brain is working harder during exercise much like the muscles are working harder your heart's working harder and it's been shown that lactate actually fuels the brain during exercise so that that lactate that's being translate um that's being transferred into circulation is being just soaked up by the brain and it's fueling the brain brain activity during exercise now another benefit of of neurons in

the brain using lactate as an energy source instead of glucose is it spares glucose it's freeing up glucose to be used by another biochemical pathway um known as the pentos phosphate pathway and this pathway uses glucose to make precursors called nadph that's needed for the production of one of the most powerful antioxidant systems in the brain called glutathione so the less glucose is being taken up by neurons to be used as energy the more it can be spared to be used in this pentos phosphate Pathway to make glutathione and this has really important relevance not

only for just you know normal brain aging right I mean if you're if you're able to use more of the lactate as energy and spare glucose and make more glutathione in the brain generally speaking that's going to be more beneficial for just normal brain aging but it has special relevance also for traumatic brain injury TBI because you know that when there's that you know bolus of damage that's that's been been done that that traumatic um brain injury then glutathione is needed the most but you're also needing you know glucose for neurons as well um and

so and and it's and it's it's it's also awful because you know asites which are usually making lactate for the neurons also become damaged during a TBI and so there's a lactate shortage for neurons um and there's been a few studies showing that a infusion um PE when there's TBI uh patients with TBI that get infused with sodium lactate this actually improves TBI outcomes and this is you know measured by the the glass cow scores so um you know generally speaking I think that this glucose sparing effect also you know there's some evidence again obviously

direct evidence with TBI outcomes that's been shown to have you know improvements in TBI TBI outcomes I'm proposing a mechanism here with glucose sparing um with respect to the with respect to lactate um lactate again also stimulates mitochondrial biogenesis animal Studies have shown this in the brain and neurons as well um we don't have direct human evidence of that but um there's no reason to think that wouldn't be a conserved mechanism so I think you know we covered the importance of brain lactate energetically speaking it's energetically favorable right neuron neurons preferentially they prefer to use

it um we talked about the glucose sparing but let's go back to the signaling molecule as ECT as we talked about earlier in the muscles we talked about it increasing glute for Transporters um it's also a signaling molecule in the brain um you know it's it's acting as a messenger it's a way for the muscles to communicate with the brain directly and um when neurons in the brain are using more lactate they're they're releasing uh a variety of neurotransmitters they release more norepinephrine for example so to help the brain working better to to have more

Focus and attention um it also signals to the brain to make more brain Drive neurotrophic factor bdnf and I mean this is a very powerful neurotrophic Factor it promotes the survival the growth and the function of neurons it plays a crucial role in neuroplasticity so this is the the ability of the brain to adapt form new connections higher levels of bdnf have been linked to improved cognitive function enhanced memory protection against neurod degenerative diseases like Alzheimer's disease um if you want to put this in Sensational words uh to explain it bdnf is the youth Elixir

for the brain and exercising muscles produce lactate to help you bathe your brain in it so um that's a little a sort of simplistic and more Sensational way of thinking about it but essentially that's what's happening when the lactate increasing bdnf in the brain um lactate is also a messenger not only in the brain but at the bloodb brain barrier um you know this is made up of tiny blood vessels we covered this in a podcast with Dr Axel Montaine so lactate signals to increase another growth factor at the bloodb brain barrier called vegf and

um this is vascular endothelial growth factor this helps grow new tiny but vessels it's called This is called angiogenesis the growth of new tiny blood vessels it helps them grow at the bloodb brain barrier it also helps repair damaged blood vessels I mean these are these are these are things that are you know important for preventing the breakdown of the bloodb brain barrier so essentially VF is increasing the vascular density and breakdown of the bloodb brain barrier is a major cause of blood of brain aging um it's a major cause of of neuroinf inflammation it

contributes to the Vicious Cycle of neuroinflammation and there's also emerging evidence that now suggests breakdown of the blood brain barrier is one of the earliest signs of dementia so again um another reason why vigorous intensity exercise through that just generation of a lot of lactate then getting to the brain getting to the bloodb brain barrier has unique benefits on overall brain brain health uh it's important to know I guess this is you know there there are benefits to high-intensity exercise on the brain that are not just exclusive to lactate right so there's increased blood flow

uh there's the improved cardiovascular fitness the release of neurotransmitters the release of endorphins you know all all of these things contribute to the positive effects of physical activity on the brain but vigorous intensity exercise I do think has some unique and very robust effects on brain health because of that lactate and so I really wanted to kind of dive deep into that so that you guys understand that you know your muscles are being pushed to work extra hard and this is then now causing adaptations in the brain that are pretty substantial in addition to lactate

exercise intensity also affects the muscles ability to produce other compounds known as myocin so these are molecules released from muscle cells that signal to nonmuscle tissues that the body is physically active you know so again it's similar to what we've been talking about with lactate myocin have anti-inflammatory they have anti-cancer effects they also participate in metabolic pathways involved in fat oxidation glucose uptake um they play a role in you know in in again cancer biology as well so generally speaking the greater the intensity of exercise the greater the myokine release again it's one of those

you're putting stress on the muscles and the the muscles are then forced to adapt and one of the adaptations is releasing myocin again um duration also matters so the harder and the longer the muscles work the greater the myokine release um some myokines are a little more sensitive to exercise intensity so is 6 was uh is one probably one of the most uh well-known myocin it was initially thought to be a pro-inflammatory cyto kind so a cyto kind that plays a role in instigate instigating inflammation um when it is produced from muscle it acts as

a mocine so it it it does play a role in inflammation but um when it's produced from muscle during exercise it's not it it's it's signaling to um other tissues to have an anti-inflammatory response and so um you'll often find a even larger production of anti-inflammatory cyto such as is 10 in response to is 6 produced during exercise irisin is another myokine it's involved in cancer protection it's involved in bone health metabolism um and and more and then there's also another well-known myokine known as onco Statin M and um that myokine sort of plays a

little more prominent role um in you know anti-an cancer effects the key here is I think that exerc um exercise intensity and or duration are really what increase myokine levels so you're going for a two or three mile run probably crank it up a little more intense right you want to be at you know at least 85% your max heart rate um so so you're not going to be really talking during that run are you going on an 8mile run maybe duration is on your side right and intensity can go down a notch since we

were just talking about cancer it keep in mind that any level of physical activity is better than none so a study investigating physical activity in breast cancer and colar rectal cancer found women who were more physically active before being diagnosed with breast cancer had about a 23% reduced risk of dying from any Cause And A 23% reduced risk of dying from breast cancer compared to those who were less active those who were more active before being diagnosed with colar rectal cancer had a 26% reduced risk of dying from any cause and about a 25% reduced

risk of dying from colar rectal cancer so being active after diagnosis had had even stronger benefits for both cancer types so these women had a 48% reduced risk of dying from any cause and a 28% reduced risk of dying from breast cancer compared to to those that were less active after diagnosis and the individuals with color rectal cancer had a 42% reduced risk of dying from any cause and a 39% reduced risk of dying from colar rectal cancer again after being diagnosed with with the cancer so I do want to talk a little bit about

you know there's a lot of mechanisms by which exercise can you know dampen cancer metastasis can um improve cancer outcomes um but there's one specific mechanism that involves tumor cells escaping from the original tumor site and then traveling into circulation to other locations other organs and you know other tissues they sort of take Camp there they grow and divide and they form a secondary tumor those cancer cells are called circulating tumor cells and that process I just described is often called cancer metastasis right um those circulating tumor cells are in circulation for a period of

time and these circulating tumor cells are very sensitive to the shearing forces of blood flow so when you exercise and blood flow increases those circulating tumor cells they actually they actually die and um this happens in a dose dependent manner so the more intense the exercise um the more sensitive they are to to sell death duration is also a key right so I mean you're talking about increasing the sheer forces both intensity and duration are key here um and and so it's really just a matter of getting that blood flow up um intensity uh duration

and um that is been shown to kill circulating tumor cells um and again this is associated with more positive outcomes with respect to cancer uh survival not only um we talked a lot about you know muscles being little chemical producing factories they're producing chemicals like lactate they're producing myocin but they also act like sponges to soak up compounds that can be harmful to the brain so skeletal muscle has the ability to take up a compound known as curine and convert it into chric acid which is a non-toxic metabolite um and it does this by increasing

an enzyme on the muscle called curine aminot transferase so this essentially reduces the amount of curine available to then be transformed into other harmful metabolites such as quinolinic acid in the brain so quinolinic acid is a neurotoxin that plays a role in depression it plays a role in schizophrenia and neurodegenerative disease um and so this is just one other mechanism by which you know exercise also seems to improve Mental Health um it's also you know another way that again exercise intensity is important here that is what is increasing that you know that enzyme that curine

aminotransferase on the muscle cells to then transport curine into the muscle so that is not um converted into the quinolinic acid um so just another another mechanism that I kind of wanted to point point out um because again intensity plays a role here with those aminotransferase Transporters soaking up more of that Kine I want to shift gears and talk about short bursts of high-intensity interval training so this is sometimes called exercise snacks exercise snacks are short bursts of vigorous intensity exercise that are Incorporated throughout the day and they it can have numerous benefits on metabolism

overall health um these exercise snacks can be as simple as doing some vigorous jumping jacks or vigorous air squats or high knees or burpee and they can be done in just a few minutes there might be some distinct metabolic benefits to exercise snacks particularly when timed around meals so performing these these you know short bursts of exercise before or so directly before or after a meal is particularly effective in controlling blood sugar levels and you know this this sort sort of thing can lead to a rapid uptake of glucose into the muscles again having to

do with increasing those glute four Transporters um it helps to lower blood glucose levels more efficiently um than staying sedentary post meals so timing exercise snacks around meals um really can help the ba the body handle sugar influx better and it helps you know utilize glucose more effectively and reduces the demand on the pancreas to produce insulin so it's um particularly beneficial for people with uh both type one and type two to diabetes in addition to the direct metabolic benefits exercise snacks can also combat sedentary Behavior so many individuals even those who engage in regular

exercise still spend a significant portion of their day sitting at their desk working being sedentary sedentary Behavior has been shown to be a modest independent risk factor for certain types of cancer um and it can also increase the risk of premature death even among Physically Active individuals so by incorporating exercise snacks individuals can kind of break up those prolonged periods of sedentary behavior and potentially further you know reduce their um cancer risk and and just have a a a variety of Bel health benefits so exercise snacks also can enhance cognitive function it's directly increasing blood

flow to the brain um you know again that that can also just have an immediate mood enhancement which affects motivation there's not a lot of direct evidence on exercise snacks in the brain um but again again of course methodologies can differ anywhere between one minute to 10 minutes um but there at least is one study showing that 10 minutes of an exercise snack does improve cognitive function so what could be a good protocol to implement let's say during your seditary time would be perhaps you know setting a timer and every couple of hours you get

up and you do a couple of minutes of you know high-intensity interval training on a very similar note there's something called vigorous intermittent lifestyle physical activity Vila it's it's somewhat similar to exercise snacks um but it takes advantage of everyday sort of situations to get your heart rate up high and to do some high-intensity exercise so for example instead of you have to take they take the stairs every day to work well instead of walking up the stairs you sprint um you're getting your heart rate high so these types of vilpas have been measured in

large numbers of people so there's a a variety of Publications um and studies that have been done uh measuring you know people's their their vilpas that they're doing and um you know just three to four minutes a day of this vigorous intermittent lifestyle physical activity has been shown to be associated with a 25 to 30% reduction in overall mortality risk um when that vpa durations increase to about 9 minutes a day it's associated with a 50% reduction in cardiovascular related mortality and a 40% reduction in cancer related mortality and these benefits extend even to individuals

who identify themselves as non-exercisers in other words these are people that are not um necessarily doing Leisure Time activity they're not going to the gym they're not going on runs but they're still engaging in these vilpas so so even those people are getting mortality reductions and you know cancer mortality cardiovascular mortality reductions with vilpas so I think that um you know that's that's also an important benefit to keep in mind so I hope you guys enjoyed this episode a deep dive into the science of why vigorous exercise is important it's important for improving cardiorespiratory Fitness

particularly people that don't respond to more moderate intensity exercise it's important for metabolic adaptations it's very powerful at increasing glucose intake into muscles it's also a very potent stimulator of mitochondrial biogenesis allowing for mitochondrial adaptations um improving not only mitochondrial volume but also fat oxidation capacity as well it's increasing mitophagy the clearance of damaged mitochondria from muscle tissue and it seems to have really unique benefits for the brain and a lot of this does come down to lactate production the metabolic stress that's induced from vigorous intensity exercise produces more lactate this lactate is getting into

circulation going to other tissues including the brain and not only is this allowing the brain to use an energetically favorable um energy source so neurons are using lactate as energy it's allowing the sparing of glucose to be used to make precursors for a very powerful antioxidant glutathione in the brain it's also acting as a signaling molecule in the brain increasing brain Drive neurotrophic Factor this is hugely important for you know not staving off neurod degenerate disease and just improving cognitive function it's increasing VF at the bloodb brain barrier you know staving off the breakdown of

the bloodb brain barrier um lactates also increasing iines in the muscle that have all sorts of benefits so I think I think we covered a lot about um the importance of vigorous exercise and also these the the vigorous exercise can be done in in short exercise snacks as well um and I think this is a really great way for schools and workplaces to incorporate uh some sort of physical activity to break up the sedentary time when people are sitting in their cubicles at their computer or sitting at their desks for um prolonged periods because just

those periods being sedentary in and of itself is a risk factor for early mortality um so again exercise snacks are a type of V vigorous exercise that can be incorporated you know into everyday life as well um as the the vilpas these are things where you're you're taking advantage of everyday situations like like sprinting up the stairs rather than than walking up them as well um so I hope you guys enjoyed this podcast and I'll talk to you soon as a companion to today's episode I've created a free evidence-based blueprint that you can download in

this guide which you can find at bdnf protocol.com you will find protocols designed to improve cognitive function and delay brain aging this guide explores modifiable lifestyle factors the tactics strategies and things you can do particularly when it comes to exercise nutrition and even supplementation to improve cognition and enhance neuroprotection many of which are at least partially mediated through increases in brain derived neurotropic Factor levels in this guide you will also find a section entitled Rhonda's protocols these Protocols are either practices I actively engage in or strategies I'm currently exploring curated specifically for their promising potential

for beneficial cognitive and neuroprotective impact these Protocols are detailed and specific everything you'd look for in a blueprint so if you're looking to dive deeper into these insights and start implying them them head over to bdnf protocol.com to get your free guide It's a valuable tool for anyone committed to optimizing their brain Health and Longevity once again that's bdnf protools.com