Fourth Pillar: Exercise

Healthy or not, exercise is important for everyone.  A balanced exercise routine isn’t just vital to fighting the progressive deconditioning that works to accelerate dysfunction.  It is also the quickest way to improve ATP-energy production and thus overall health.  This is because skeletal muscle is capable of complete regeneration.  Traditional cellular turnover occurs through cellular division that, at a minimum, maintains the DNA and other characteristics of previous generations of cells.  But as cells go through their regular life cycle, there is also increased risk of additional deletions and damage that can cause further impairment.

In contrast to cellular division, correctly performed resistance or weight bearing exercise with a focus on muscle building causes “good” trauma” to the muscle, in the form of small tears.  As the muscle begins the healing process, skeletal muscle stem cells and non-skeletal muscle stem cells are used to repair and build up the muscle tissue.  These stem cells are newly generated cells more likely to contain healthier functioning Mitochondria and in greater numbers.  This increase in both quantity and functional capacity of Mitochondria can increase overall ATP-energy production, providing the energy necessary to combat deconditioning.  This is why physical therapy is now considered an important part of treatment protocols for all Mito patients.  Therefore, when it comes to improving overall Mitochondrial capacity to produce ATP, weight bearing exercise with a focus on muscle building can provide the biggest bang for your buck.


Are you huffing and puffing while exercising? STOP! Yes, stop exercising and catch your breath. Especially with Mitochondria impaired individuals, if you are breathing heavy enough that you can’t easily carry on a conversation, you are actively digging yourself an energy hole that could trigger an energy crisis and potentially be damaging cells and tissue in the process.

Just as there have been wrong or misleading information in regards to what constitutes a healthy diet, there is just as much misleading information about what is truly health-promoting exercise. Part of the problem lies with the overly broad use of the terms Aerobic and Anaerobic in describing vastly different concepts.

Aerobic:  Defined as: relating to, involving, or requiring free oxygen.

Aerobic Energy:  (Also referred to as Aerobic Oxidation)  ATP-energy provided in the presence of sufficient oxygen molecules that are required to both initiate and complete the Electron Transport Chain (ETC).  This is the energy process that produces the largest amount of ATP-energy per cycle.

NOTE 1:  The source of Pyruvate / Acetyl-CoEnzyme A (Acetyl-CoA) used in Aerobic energy production can make a huge difference in ATP output. Fatty Acid Metabolism (Beta Oxidation) also requires oxygen and will actually generate 17 additional ATP during the conversion of Fatty Acids into Acetyl-CoA (as opposed to Glycolysis only producing 2 ATP). The Acetyl-CoA is then used to “turn” the Krebs cycle, which then feeds the ETC to generate even more ATP. Fatty Acid Oxidation (using fat as your fuel source) provides eight Krebs cycles and causes the ETC to produce exponentially more ATP per Fat molecule, on average 130 ATP. In contrast, Glycolysis (using Glucose from carbs/sugar as your fuel source) only provides enough Acetyl-CoA for two Krebs cycles resulting in significantly less ATP production through the ETC, on average 68 ATP. Thus a Fat molecule can provide nearly TWICE as much ATP as a Glucose molecule and Fat also burns much cleaner, meaning less reactive oxygen species!

Anaerobic:  Defined as: relating to, involving, or requiring an absence of free oxygen.

Anaerobic Energy:  (Three Forms: ATP-CP, Glycolysis, and Fermentation / Lactic Acid)  ATP-energy provided in the absence of, or not requiring, adequate oxygen.  All forms of Anaerobic Energy are short-lived cycles that cannot be sustained for extended periods of time.  Very little ATP is produced to be used for energy.  Demand for ATP often exceeds ATP-generating capacity.  This can cause the creation of an ATP-energy deficit (unless sufficient oxygen is present to initiate the ETC and produce ATP through Aerobic Oxidation).

Energy Transfers Associated with Energy Demands:

The very state of being alive carries with it an energy demand.  Those who are severely impaired in ATP can often feel winded with the littlest physical activity.  (NOTE:  becoming easily winded can also be a sign of other significant health issues that need to be evaluated by a qualified healthcare provider.)  When we begin any type of physical activity, the body cycles through several different forms of energy delivery.  The duration of each of these delivery systems depends on several factors.  However, overall Mitochondrial capacity to supply ATP has a huge influence over endurance.

It is important to note that the most ATP is only able to be produced in the presence of sufficient oxygen.  Without enough oxygen, the most efficient form of ATP production cannot take place (the Electron Transport Chain).  Therefore, cells are forced to use less efficient processes that cannot produce sufficient ATP to keep up with a continued physical demand.

Energy Transfer Mechanisms:  The durations indicated below are averages based on healthy individuals.  These times will differ between individuals.

Phosphagen System – ATP / CP Phase (approx 10 seconds):  With initial physical demand, muscles depend on locally stored Adenosine Tri-Phosphate (ATP) and Creatine Phosphate (CP).  ATP releases one phosphate and becomes ADP.  The ADP can use the phosphate from available CP to regenerate ATP.  No carbohydrate or fat is used in this phase. It is anaerobic in function (no need for oxygen) but does not result in lactic acid build-up.  Although this is the quickest way to generate ATP, the available energy from muscularly stored ATP and CP is extremely short-lived; approximately 10 seconds.  Thus fatigue rapidly occurs.

Glycolytic System (approx 30 seconds to 2 minutes):  As continued energy demand exceeds the Phosphagen System capabilities, Glycolysis is initiated.  Glucose, from either blood glucose or muscle glycogen, is converted to Pyruvate. During this conversion, each molecule of glucose is converted to a net gain of 2 ATP.  Glycolysis is the second quickest way to generate ATP; however, the total ATP produced is extremely low.  Although Glycolysis occurs throughout the body at any given time, it is the main source of ATP within a working muscle for approximately 30 seconds to 2 minutes.

From this point, the Pyruvate generated during Glycolysis can take two pathways; conversion to Acetyl-CoEnzyme A in the presence of sufficient oxygen or conversion to Lactate when oxygen is scarce.

Aerobic Oxidation (over 2 Minutes):  Only if sufficient oxygen is present in the cells, as energy demand exceeds the ATP being produced in the Glycolytic System, Acetyl-CoEnzyme A (or Acetyl-CoA) enters the Mitochondria for oxidation via the Krebs Cycle and the Electron Transport Chain (ETC).  This is the slowest, most complex energy producing cycle, but produces 18 times more ATP than Glycolysis, averaging 36 ATP for each Glucose molecule broken down.  This efficient and effective production of ATP via aerobic metabolism is key to endurance and overall health.

NOTE 2:  As discussed in the note above, Fat burning (Fatty Acid Oxidation) can be used as the primary source to feed Aerobic Oxidation instead of glucose. This process requires that both oxygen is abundant and also that glucose is scarce. When blood glucose and muscle glycogen become depleted, the body naturally shifts to production of Acetyl-CoA to feed Aerobic Oxidation. (Exception: there are disorders such as Fatty Acid Oxidation disorders that can significantly impair utilizing Fat as a primary fuel source and thus require carbohydrates in order to feed ATP production.)

Anaerobic:  When there is NOT sufficient oxygen present, the ETC is bypassed and energy production occurs through fermentation.  This form of energy production has limited ATP generating capacity and increased fatigue factor.  Over time, it can also be detrimental to your health. Oxygen acts as the Alpha and the Omega, required to donate electrons in the beginning and accept electrons at the end of the respiratory chain.  Bypassing Mitochondrial function prevents the “exercise” of your Mitochondria.  As oxygen and available ATP continue to diminish, microscopic cellular damage begins to occur. As this damage builds with repeated, extended anaerobic function, cellular damage becomes tissue damage, which can eventually lead to functional failure.

Incorrect Perceptions of Aerobic vs Anaerobic Exercise:

The term aerobic exercise has been used synonymously with “cardio” exercise and is described as exercises that get your heart, and thus your blood, pumping. It is assumed that increasing cardiac output necessarily means increased oxygen delivery to fuel Aerobic Oxidation. This is somewhat true, but as shown under energy transfers, performing “aerobic exercise” does not necessarily equate to cells using Aerobic Oxidation to deliver ATP.  When you begin breathing heavy, your brain has received a signal that there is not sufficient oxygen to sustain Aerobic function.  In response, your autonomic nervous system triggers an increase in both breathing and heart rate in an effort to compensate.  As exercise demand continues, the system cannot deliver oxygen quickly enough to continue Aerobic Oxidation.  So the “aerobic exercise” continues but the cells are forced to function Anaerobically in an attempt to continue to deliver ATP, albeit at a much lower ATP output.  At this point, you are utilizing more energy than you are capable of producing… effectively creating an energy deficit.

Extended and/or repeated ATP deficits to tissue can cause hypoxic damage to cells, tissue and nerves. This doesn’t mean someone can’t work to improve cellular aerobic capacity; however, if ATP production is impaired, it is more likely that sustained “aerobic exercise” with anaerobic cellular function will end up causing more damage than the benefit sought.


*  See Precautions and Considerations below.  Always check with your healthcare provider prior to starting a new exercise routine.


Especially for those untrained or deconditioned persons, resistance or weight training can reduce lactic acid thresholds and can increase aerobic capacity through increased Mitochondrial respiratory capacity.  As discussed above, the stimulated muscle growth adds to the number of cells, increasing the total number of Mitochondria and often shows improved Mitochondrial function.

In order to gain the Mitochondrial advantages of resistance or weight bearing exercises, it is important to differentiate between muscle hypertrophy and muscle hyperplasia.  Hypertrophy is an increase in the size of cells.  In regards to muscle size, hypertrophy is generally brought about by low weight, high repetition training that fails to sufficiently challenge the muscle.  The subsequent increases in muscle size are due largely to swelling of muscle cells / fibers.  This does not necessarily increase overall Mitochondria and actually results in a dilution of Mitochondria amongst the expansion of the cells.  (Note: Though some exercise is generally better than none, there is very little benefit to low weight, low repetition.  It serves more to fatigue the muscle but doesn’t sufficiently work the muscle to produce value inherent to muscle building.)  Alternatively, Hyperplasia involves an increase in muscle size by increasing the total number of cells that make up the muscle.  Hyperplasia is accomplished through utilizing sufficient weight (loading), generally with fewer repetitions, that challenges the muscle adequately to cause tiny tears in the muscle fibers.  These little injuries (that will cause soreness) stimulate stem cell repair and result in improved muscle strength and increase both cell numbers and overall number of Mitochondria.  (Note:  Low weight verses sufficient weight / loading is a very individualistic value and can fluctuate based on functional capacity at the time the exercise is performed.)

As key as muscle building is, if you are struggling with energy issues and pain, exercise can be a quagmire.  Weakness and fatigue and the aftermath of physical activity is a huge hindrance to most people who struggle with exercise.  One must learn to balance appropriate rest, nutrition, and energy conservation that provides the necessary energy to accommodate working out.  Also keep in mind, even with slow and steady weight bearing exercises, you are still utilizing energy and you might find yourself beginning to breath heavier as demand increases.  This is your sign to stop, take time to catch your breath and evaluate your progress.  Constantly evaluating when to exercise, how to exercise and how much to exercise will help balance your efforts and will play a key role in facilitating continual progression instead of hitting your wall and the setbacks from the wrath of overdoing it.


Once you are no longer fighting a constant energy crisis, you can consider adding an element of aerobic exercise to your workout routine.  The key to successful aerobic exercise is constant awareness of breathing patterns to ensure you are avoiding prolonged anaerobic cellular function.  A great aerobic workout that utilizes this energy conserving, oxygen optimizing concept is called HIIT Training (High Intensity Interval Training).  For beginners, HIIT Training is probably most safely done on a stationary or recumbent bike, or outside on level surface like on a running track.  If falling or fainting are not at issue, an Elliptical or Arc Trainer, Stairmaster or Treadmill could be used.

HIIT training (or in other countries known as HIT) has been studied across several different countries and has consistently shown benefits for Mitochondrial health and improved overall Mitochondrial capacity.  Additional studies have found improved hormone balancing and better mobility and function in aging populations.  Still more research has shown that HIIT Training naturally increases production of Human Growth Hormone (HGH).  Studies have shown natural releases of HGH can help regulate metabolism, increase muscle mass and decrease body fat, improve sleep, boost mental well-being and improve immune function.  Other studies have shown improved health and healing capacity for bones, collagen, muscle and other tissues, in addition to improvements in overall physical functioning.

Before we dive into how to do HIIT, watch this excellent video from Investigative Reporter Anja Taylor of Australia’s ABCTVCatalyst. She interviews several international researchers on Mitochondria and how they are using HIT to improve everyone from athletes, to the aging and even a genetic Mitochondrial disorder!

Fit In Six Minutes, ABCTVCatalyst, 27:55

THE BASICS OF HIIT:  HIIT consists of alternating between highly intense effort and recovery intervals.   As with any exercise, you want to warm up first to prevent injury.  The High Intensity portion consists of a quick-burst or sprint of all the effort you can safely give, for as long as you can safely sustain the activity, BUT FOR NO MORE THAN 30 SECONDS. (If you are able to do more than 30 seconds, you probably aren’t pushing yourself hard enough.)  The Recovery Interval consists of light activity for approximately 4-1/2 minutes.  During this time, do slow walking or pedaling and focus on breathing; do not immediately sit down after the high intensity interval.  If your heart rate and breathing have not normalized at 4-1/2 minutes, continue the recovery interval until they do.

NOTE:  In the video, one researcher was having participants do 8 second sprints on a stationary bike, with 12 seconds of recovery for a total of 20 minutes of exercise and still observed huge gains in function. So start where you can and do what you are capable of doing.

Start off with one set and work your way up to more as your overall ability improves.  The point is not to overdo or to cause injury.  Be diligent in listening to your body and adjusting to your current abilities.


  • Check with your healthcare provider to discuss additions or changes to your exercise routine.
  • Certain medical conditions might require working with a physical therapist first to establish the type of exercises and precautions that will protect you from injury.  This includes, but is not limited to, people with weak bones or connective tissue disorders.
  • Make sure you are educated on the exercises you are doing.  Form is important to working the right muscles and preventing injuring to joints and connective tissues.
  • Similarly, make sure you are educated on the equipment you are using.  Don’t assume the last person left the equipment set up properly for you.  Ask gym staff for training on how to set up each piece of equipment and on proper body posture to avoid injury.  Then, each time, take a moment to make sure everything is just right before proceeding with the exercise.
  • If the equipment has a pivot point, that pivot point should be lined up with the pivot of the associated joint (a/k/a the elbow, knee, etc.) while allowing for proper posture from the head through the spine and to the toes.
  • POSTURE – Yes, I am mentioning it again.  Proper posture
  • Use slower repetitions during muscle building.  Quick and jerky movements can over stress muscles and connective tissue, increasing the risk of injury.  Also, slower repetitions allow for proper breathing through the movement (see below).
  • BREATH – make a conscious effort to breath through your exercises.  You might be surprised at how much you hold your breath, especially with muscle building exercises.  The more oxygen you can deliver to the tissues, the better the performance.  Regulate your breathing so that you are exhaling during the the load bearing portion of the exercise (when you are contracting the muscle to push or pull the weight), and inhaling during the unloading portion (releasing the weight back to your starting position).

Things to ask yourself each time before and during exercising:

  • Am I strong enough and have I conserved enough energy to attempt training today?
  • What is the safest form of exercise based on my current condition and abilities?
    • HIIT Training, options can include sprints, biking, stationary or recumbent bike, treadmill, elliptical, etc.
  • How long should I workout?  /  Should I continue my workout?  (This should be a continuing consideration.)
    • HIIT Training:  How long should my High Intensity Challenge Interval be?
      • The Challenge Interval should be based on individual ability and can be much less than 30 seconds, but should not be more than 30 seconds.  If you are able to do more than 30 seconds, you probably aren’t pushing yourself hard enough.
    • HIIT Training:  How long should my Recovery Interval be?
      • The goal of the Recovery Interval is to regain both normalized heart rate and breathing so energy production can be maximized through sufficient oxygen delivery.
      • If your Recovery Interval is becoming significantly longer than your previous one, it is time to stop.
  • The answer to these questions will change from day to day, and even moment to moment.  Remember, when trying to build back aerobic effort, you aren’t attempting to do all you “can” do, you are only attempting to do all you “should” do.  More isn’t always better.
  • Keep in mind that your ability will fluctuate.  And as exciting as it is to see progression, you will eventually plateau in how much weight you can do.  This is completely normal, even if you aren’t working to overcome Mitochondrial Dysfunction.  Don’t add to or perpetuate a weak day (or even a few weak days)  by stressing over the inevitable moments of weakness.  Give it all you can.  Then evaluate any potential causes and make adjustments as necessary.
    • Are you properly hydrated?
    • Have you gotten enough sleep / rest?
    • Have you been under any recent physical, mental / cognitive, or emotional stress?
    • Did you slip off your diet and eat something you know negatively effects you?
    • Did you miss taking any of your supplements?
    • Maybe you need a little iron?  Might be time for some red meat.  (Especially women during their cycle.)
    • Have you been exposed to something that might have triggered your immune system? (This is a huge energy drain and weakness and an increase in symptoms could be your first sign you are fighting something.)
    • Over time, you will become more in-tune with your body and start figuring out other triggers you can add to this list.


MORE TIPS COMING SOON!  We are also working on exercise tip videos.  Subscribe to our YouTube channel to get updates on new uploads.


Several things happen when you exercise.  Initially, ATP production may increase during increased delivery of oxygen.  However with continued effort, eventually energy demand will exceed oxygen delivery and the switch will be made to anaerobic cellular respiration.  (Yes, “aerobic” exercise can actually, eventually, throws you into anaerobic function.)  This switch triggers the creation of lactic acid in a highly inefficient process of generating minimal ATP-energy.  This lactic acid is responsible for the immediate swollen, stiff and sore sensations following physical activity (the level of activity required to trigger this effect depends on the individual’s efficiency in utilizing available oxygen).

Another effect of exercise is muscle stressing that can cause rips and tears to muscle fibers.  In effect, you have damaged the muscle.  However, muscle tissue is beautiful and dynamic, inherently capable of not only enduring such damage, but thriving on it. Muscle tissue contains resident stem cells called Satellite cells that can immediately respond to such injuries and, often joined by non-muscle stem cells, not only regenerate the damaged tissue but also build the muscle to become stronger, primed to offer more efficient functional capacity for future use.

But the pain and recovery time can sometimes discourage the consistent effort needed to achieve optimal results.  Important aspects of achieving peak results from exercise efforts include:  avoidance of and recovery from lactic acid build-up, replenishment of spent glycogen stores and other nutrients and electrolytes, and protection of and increased availability of protein to assist in muscle repair and muscle building.  Each of these can be addressed through post-workout recovery efforts.

HYDRATION:  Hydration is important from the moment you wake up in a dehydrated state from the night before, through every aspect of your day and especially during any exercise.  Hydration should focus largely on water, but can be bolstered by the addition of low- to no-carb amino acid powders (that contain all the amino acids, not just BCAA’s) or by making your own healthy hydrating drink like homemade Aloe Water.


RECOVERY:  There are a lot of recovery products on the market.  Most have a heavy emphasis on Glycogen.  But as discussed above, recovery requires so much more.  Easily digestible protein and amino acids are the best way to give your muscles what they need to recover and repair, building bigger, stronger, healthier cells to help propel you forward on your road toward optimal health.



More information on muscle function, muscle dysfunction, spasticity, weakness and paralysis can be found on the page “Understanding Muscle Function.”



MUSCLE BUILDING (Resisting / Strength Training)

(2003) The impact of resistance training on distance running performance.

(2006) Effects of Exercise on Mitochondrial Content and Function in Aging Human Skeletal Muscle.

(2006) Increased muscle oxidative potential following resistance training induced fibre hypertrophy in young men.

(2010) Resistance Training Increases Muscle Mitochondrial Biogenesis in Patients with Chronic Kidney Disease.

(2014) Resistance training increases skeletal muscle oxidative capacity and net intramuscular triglyceride breakdown in type I and II fibres of sedentary males.

(2015) Resistance Exercise Training Alters Mitochondrial Function in Human Skeletal Muscle.

(2017) Resistance training to improve type 2 diabetes: working toward a prescription for the future.


(1993) High intensity training-induced changes in skeletal muscle antioxidant enzyme activity.

(2002) The scientific basis for high-intensity interval training: optimising training programmes and maximising performance in highly trained endurance athletes.

(2007) Mitochondrial Myopathies: Exercise and Nutrition. (VIDEO presentation by Dr. Mark Tarnopolsky, 51min 38sec)

(2007) Two weeks of high-intensity aerobic interval training increases the capacity for fat oxidation during exercise in women.

(2007) High-intensity Interval Training: A Time-efficient Strategy for Health Promotion?

(2008) Metabolic Adaptations to Short-term High-Intensity Interval Training: A Little Pain for a Lot of Gain?

(2008) High-intensity aerobic interval training increases fat and carbohydrate metabolic capacities in human skeletal muscle.

(2010) A practical model of low-volume high-intensity interval training induces mitochondrial biogenesis in human skeletal muscle: potential mechanisms.

(2011) An acute bout of high-intensity interval training increases the nuclear abundance of PGC-1α and activates mitochondrial biogenesis in human skeletal muscle.

(2011) Low-volume high-intensity interval training reduces hyperglycemia and increases muscle mitochondrial capacity in patients with type 2 diabetes.

(2012) Physiological adaptations to low-volume, high-intensity interval training in health and disease.

(2013) Improvements in exercise performance with high-intensity interval training coincide with an increase in skeletal muscle mitochondrial content and function.

(2014) Novel, high-intensity exercise prescription improves muscle mass, mitochondrial function, and physical capacity in individuals with Parkinson’s disease.

(2014) A Randomized, Controlled Clinical Trial of Exercise in Patients with Spinal Muscular Atrophy: Methods and Baseline Characteristics.

(2015) Adaptations of skeletal muscle mitochondria to exercise training.

(2016) Effect of High-Intensity Interval Versus Continuous Exercise Training on Functional Capacity and Quality of Life in Patients With Coronary Artery Disease: A RANDOMIZED CLINICAL TRIAL.

(2016) Twelve Weeks of Sprint Interval Training Improves Indices of Cardiometabolic Health Similar to Traditional Endurance Training despite a Five-Fold Lower Exercise Volume and Time Commitment.


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