Exercise Heals Mitochondria

We spend a lot of time on this website talking about nutrients to heal the mitochondria, which I believe are the foundations of health, but we do not talk nearly enough about the role of exercise in this process. Exercise is integral to health, not just because it staves off obesity, cardiovascular disease, and diabetes – the trifecta of modern illness, but because it is a critical signal for mitochondrial functioning; one that no amount of dietary supplementation can replace.

For those who know me personally, I have long been a proponent of using exercise to treat all that ails me. I have been an athlete for the better part of my entire life. From childhood through college, I was a swimmer and then played water polo for a good 15 years thereafter. This was followed by spin classes, running, and other forms of general fitness, then by CrossFit, and finally, over the last 7 or so years, well into my fifties, I have become a competitive powerlifter. I am someone who likes to work out, who likes new challenges, and who likes being strong. That activity base, while it doesn’t prevent illness or injury, I believe it does allow one to survive illness and injury more adeptly.

To that end, I have used exercise along with nutrition and other more holistic modalities to treat every illness I have ever encountered. While it is true there have been times in my life when I could perform only minimal exercise, a slow ride on a stationary bike or slow (sometimes exceedingly slow) walk in the neighborhood, I have always done what I could to keep moving. With each surgery or  illness, I push myself to movement as soon as I am capable. If I do not move, recovery, it seems, takes longer.

For me, if I can move, even minimally, then I know I can heal. I track that healing based upon how well or poorly I move. And there are times when I have moved very poorly. These last two years, for example, I have been dealing with family and personal health issues that, for a time, all but crippled my work capacity physically and mentally. (Regular readers of HM might have noticed that I have not written much lately.) During this period, I could only handle a few minutes of exertion at a time with significantly reduced weights. This is compared to my normal 90-120 minute workouts with some damned heavy weights. To compensate, I divided my workouts across the day, with just a few sets of light weights or easy body weight movements at a time. It wasn’t ideal, but it kept me moving.

My morning walks were also affected. While I normally walk slowly, these walks have always been more for relaxation and contemplation than anything else, for months I was so slow and uneven that at one point a gentleman on a bike came up to me and said: ‘that’s okay, any pace is a good pace.’ I am sure he thought he was being positive, but I wanted to punch him nevertheless. Truthfully though, I was not doing well. I was walking like a little old lady, unbalanced with a short gait that was exceptionally slow and labored. I just kept shuffling along though, knowing that if I had any hope of recovery, I had to keep moving.

Eventually, I did begin to recover and both the work capacity in the gym and the walking improved (as did cognitive capacity – thankfully). I believe, in addition to everything else I was doing to recover my health, exercise played an important role. A large and growing body of research supports this. Exercise is absolutely critical for mitochondrial functioning. There is no way around it. Yes, we need to supply the mitochondria with nutrients, as a good percentage of mitochondrial dysfunction emanates from poor diet and a lack of nutrients, but we also have to supply them adequate movement and exercise. If we do not, no amount of nutrient support or ‘rest’ will provide sufficient healing.

Mitochondria and Energy

We all know that exercise is good for us. What is often missed in the push to use exercise for weight management and other issues, is the role that exercise plays on metabolic health, and more specifically, the role exercise plays on mitochondrial functioning.

Recall from high school biology (and from the library of posts on this site), the mitochondria are responsible for converting components of the foods we eat into ATP, the energy source that all cells require to function. They are essentially energy factories. This energy is absolutely requisite for the efficient functioning, and ultimately, survival, not just of the cells, but of the tissues and organs in which they reside. Limit ATP by a lack of macronutrients/starvation (not as common in the western world, except with illness), a lack of micronutrients – vitamin/mineral malnutrition (very common with the modern diet), or by unending toxic exposures such as pharmaceutical, agricultural, environmental and industrial toxicants (also very common) and ATP production suffers. As it does, all of the systems that are energy dependent, life essentially, begin to degrade.

Among the easiest ways to improve mitochondrial function are to increase mitochondrial nutrient intake and reduce toxicant exposure. In other words, clean up one’s diet and environment. Another way to improve mitochondrial function, although perhaps not as easy as the first two, especially if one is ill or has been ill for a long time, is to move. Movement forces the mitochondria to function more efficiently in order to provide more energy. It does this by several mechanisms that will be discussed below. For a moment though, think about this more simply. Which requires a more efficient production of energy, the contracting and active muscle or the immobile muscle? A contracting muscle, of course. This means that a key element in mitochondrial energy production is demand. Where there is demand, there will be supply, at least to a point (and provided nutrient resources are available). Conversely, where there is limited demand, there is no need for the efficient supply of energy. Any old pathway will do. While this is oversimplification to be sure, it is a fairly accurate one. The mitochondria will produce energy where energy is needed most and limit energy production where and when it is not needed. From this perspective, we can see how sedentary lives might lead to problems with mitochondrial functioning and by association, how the immobility of illness might hinder recovery.

A Moving Body Moves Nutrients

Just how exactly does exercise benefit the mitochondria? To begin with, exercise increases the number of mitochondria per cell (mitochondrial biogenesis) in the muscles and enhances how the mitochondria metabolize foods into energy. It improves oxidative metabolism (also called oxidative phosphorylation or OXPHOS), the mechanism by which we create the most ATP (~30-100 units of ATP per molecule of glucose or fat, respectively with OXPHOS, versus the 2-4 units that are produced outside the mitochondria via glycolysis). Exercise requires more ATP, which in turn, requires better oxygen and nutrient flow. The improved energetics in turn create better communication networks between mitochondria, better regulation of mitochondrial morphology (shape), and importantly, improved waste management procedures known as mitophagy or autophagy (removal mechanisms for depleted or dysfunctional mitochondria – a outcome many proponents of fasting strive for). In other words, the exercising muscle must produce more energy, more efficiently than the sedentary muscle and it must remove waste more quickly and so it does. This requires as many energy factories as possible that run as efficiently as possible. The body compensates to meet these demands. The beauty of this compensation is that it spills over to greater efficiencies system wide. Of course, all of this requires proper nutrition, but proper nutrition alone, absent exercise, will not net the same improvements in oxidative capacity. In fact, immobility does as much or more to damage oxidative capacity as poor nutrition. Exercise does all of this and more. For a wonderful review, see Exercise is Mitochondrial Medicine for Muscle.

Immobility Equals Stagnation

Just as exercise improves mitochondrial functioning, immobility degrades it. With immobility, we get stagnation e.g. reduced blood flow, reduced oxygen capacity, poor nutrient utilization, and importantly, reduced muscular strength, which, over time feeds on itself. Called sarcopenia, the muscle wasting of immobility leads to a number of deleterious metabolic changes involving reduced mitochondrial capacity and poor immune and inflammation management. Sedentary lifestyles initiate the same patterns, only more slowly, and if one was sedentary before facing a period of immobilization because of illness, accident, or surgery, the deleterious effects of immobility on the muscle and metabolism develop much more quickly and are more pronounced.

When muscles are not used, they waste away and underlying metabolism shifts dramatically from one that is anabolic to one that is catabolic. This goes beyond just a loss of visible muscle or strength, with immobility there are significant metabolic changes that affect every aspect of health. With sarcopenia, for example, whether from complete immobilization or just an extended sedentary lifestyle, there is a shift in the balance between protein synthesis and degradation that favors protein degradation. In other words, because the muscles are not being used, and energetic capacity is reduced, the body derives its energy and proteins from the degradation of muscle rather than from diet (and if diet is poor, the problem is exacerbated). Indeed, with that shift favoring protein degradation for energetic capacity, there is a concomitant loss in metabolic (oxidative) capacity.

It Doesn’t Take Much To Improve Mitochondrial Function

A study published in August 2022, found that repeated contraction of the soleus muscle in the calf, improved body-wide metabolic capacity. Specifically, contraction, in this case performed as heel raises while seated, improved mitochondrial oxidative metabolism, the key component of ATP production. Imagine that, simply contracting the calf muscle improved energetic capacity. I suspect contraction of other muscles might have a similar effect, though that was not tested. I should note, the test subjects were sedentary and largely deconditioned. This begs the question, would this type of activity work to improve the oxidative metabolism of individuals who were bedridden but mobile? Possibly, if done consistently.

A study I found years ago, but have long since lost and am unable to find again, showed that if a therapist ‘exercised’ the arms and legs of patients who were unconscious or otherwise unable to move themselves, the rate of muscle loss was diminished and other metabolic parameters were improved, as were the overall outcomes of the patients. I do not remember the specific exercises or the time frame, but I recall being struck by the size of the difference between those patients who were exercised by a therapist and those who were not.

Extended Sitting and Mitochondrial Deterioration

Recently, researchers tested the effects of an extended period of sitting in healthy individuals. The results were dramatic, after just 3 hours of sitting (something we all do, every day), endothelial dilation decreased significantly. The endothelial cells line the heart and vasculature and respond to and initiate changes in blood flow by dilating or contracting. In other words, failing to move reduces the diameter of the vessels limiting blood flow. This makes sense, immobility does not require the same amount of oxygen and nutrients that movement or exercise does, so the body conserves when and where it can.

Personally, I found this to be true as well. When I was ill, my blood pressure would spike, particularly after sitting for extended periods. If did few minutes of cardiovascular exercise, jump rope or sprints on the bike were my go to exercises for this, I could lower my BP for an hour or two. My slow walks were not sufficient to lower BP, at least not acutely, although I suspect they helped in other ways. To drop my BP immediately, I had to sprint. I was feeling rotten, had no desire to move, but I knew that if I moved, even if only for 2-3 minutes, I could manage whatever was happening to cause the spikes in BP.

Remember, I have exercised regularly for decades and have my nutrients on board, so my body had not been totally deconditioned from the illness. Someone who has been deconditioned by illness should not try sprinting as their first foray into physical activity. Exercise after prolonged immobility must be done judiciously and one’s tolerance to it must be built up slowly because not only does prolonged immobility make muscles more prone to damage when exercise is re-initiated, when overdone, it may tax the mitochondria beyond their capacity to function properly. When mitochondria are stressed, there is trend towards increased lactate and poor lactate recycling. Lactate can be used to make ATP if the mitochondria are working well, but when they are not, it builds up and causes all sorts of problems. This is seen in individuals with ME/CFS, but may be also seen in a variety of other conditions. Of note, the higher lactate in ME/CFS has been linked to problems with the thiamine-dependent enzyme, pyruvate dehydrogenase complex suggesting that thiamine would be useful. In general, insufficient thiamine leads to poor energy metabolism (excessive fatigue due to the very real diminishment of ATP capacity) and excess lactate. Correcting this pathway would be a key factor in being able withstand any amount of physical activity.

Other Mitochondrial Improvements Associated with Exercise

Cardiolipin Internalization

This one, though technical, is really quite cool. Along with the shift towards better energetic capacity and more efficient waste removal, exercise regulates bleeding and clotting and possibly the propensity towards some autoimmune conditions by something called cardiolipin. Cardiolipins are phospholipids (phosphate and fat) normally located at the inner mitochondrial membrane. They make up about 20% of the fatty content of the mitochondrial membrane. Cardiolipins help regulate all sorts of mitochondrial processes including, OXPHOS (ATP/energy production), mitochondrial morphology, and mitophagy. Importantly, cardiolipin is integral to the management of clotting, but only when they remain inside the mitochondrial membrane. Once the cardiolipin molecules park themselves on the outside of the mitochondria, as they tend to do more frequently with immobility and as mitochondrial capacity wanes in the face of illness or toxicant exposure, all bets are off. Extra-mitochondrial cardiolipin is recognized as a threat and a battle begins. Antibodies against cardiolipin are produced in greater and greater concentration (antiphospholipid antibodies) to track down and remove these molecules. The net result is an ‘autoimmune’ reaction that elicits increased clotting. Exercise modifies this pattern favorably, sending the cardiolipin molecules back inside the mitochondria where they belong. This suggests that exercise or lack thereof, may play an important role in autoimmunity and clotting disorders.

Cancer Reduction, Better Immune Regulation, and Improved Brain Function

As if all of that were not enough to convince us that exercise is needed to maintain mitochondrial health, new research, using multiple modalities (cell culture, mice, and human data), found that regular exercise provided a sort of metabolic cancer shield by directing nutrients towards organs and away from tumors. From the study:

…exercise-induced metabolic reprogramming of organs transforms them into metastatic-resistant metabolic microenvironments by limiting nutrient availability to the cancer cells thus creating a metabolic shield.

Much of this transfer of nutrients is mediated by cytosolic nutrient sensor called mTOR that coordinates energy consumption and production between the cell and its mitochondria. With cancer cells, mTOR is upregulated. It is also upregulated with regular exercise and this is believed to be the mechanism that diverts energy away from the cancer cells towards other cells, tissues, and organs. This does not mean that one can eliminate the risk of cancer altogether with exercise, as there are many contributors to oncogenesis – poor nutrient intake, excess sugar, and toxicant exposure to name but a few, just that when one exercises, nutrients are diverted away from cancer cells and their mitochondria towards the healthier mitochondria in active tissues/organs. This is a good thing.

Exercise or physical activity in general, also upregulate host immune response to cancer and other toxicants or illnesses through multiple pathways including vasodilation (enhanced transport of nutrients and oxygen to the exercising muscles) and improved immune cell function via the recruitment macrophages, natural killer, and CD8+T cells. Exercise also streamlines cellular/mitochondrial waste management processes and inhibits the capacity of tumor cells to adhere to endothelial cells (again preventing the leakage of toxicants into the system). It is really quite remarkable what a little movement can do for the body.

Finally, while it is commonly appreciated that exercise favorably influences both cognitive and affective function, it appears that one of the main mechanisms is by optimizing mitochondrial function and maximizing mitochondrial energetics. As we have discussed throughout this article, compared to rest, exercise demands a more efficient production of energy. Signals from the body to the brain and back again manage this energy production. The signals are different with immobile versus active muscles, such that inactive muscles can negatively skew energy metabolism in the brain. This then drives neurodegeneration. Over the years, researchers have identified many of these molecules, named ‘exerkines’ that influence brain health by directly modulating mitochondrial bioenergetics, content, and dynamics. Since exercise improves cognitive function in patients with neurodegenerative disorders, it is entirely possible that exercise, along with nutrition, will, if not prevent, at least substantially risk of these conditions.

But, What If I Cannot Exercise or Move?

That is the million dollar question. What if one has been chronically ill, bedridden and simply does not have capacity for exercise? This one is complicated and becomes increasingly so as the illness and immobility persist. As I mentioned before, mitochondrial nutrients must be on board first. Top among them, but often disregarded, is thiamine. Thiamine is the gatekeeper to energy metabolism and must be consumed in concentrations commiserate with demand – healing from illness increases the demand considerably. Healing takes energy. Energy takes thiamine. So, before beginning any program, support mitochondrial nutrients. Do the research. We have dozens on articles on this site.

The next step would be to disregard everything you think you know about exercise, everything you were able to do before you became ill and start with improving oxidative metabolism – mitochondrial capacity to use and produce energy. To do that, we have to move blood, oxygen, and nutrients, that’s it. That is the only goal and all that requires is muscle contraction and breathing. Breathe into a muscle, contract it, breathe out and release. Frankly, deep breathing alone or contracting alone can be helpful, but I find combining the two is more useful. Start there. That can be done laying or sitting and can adjusted according to one’s tolerance and capacity. Take it slowly and build up from there.

I will write more about rehabbing mitochondrial capacity in a subsequent article, for now though, know that sometimes the simplest activities can be the most effective. The key is consistency. Whatever activity you choose, do it consistently, at the same time or times everyday. As you build tolerance, increase. It will be slow and tedious, but that is what is necessary to improve.

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Photo by Bruno Nascimento on Unsplash.