As a cyclist and former elite runner, my two favorite words in the English language are “mitochondrial biogenesis“. My least favorite are “mitochondrial myopathy“, the thought of which fills me with horror, as well as great compassion for those afflicted with one of the rare diseases that fall into this category. Mitochondria is energy. Energy is life. Matter without energy is a state of lifelessness. Your mitochondria are the microscopic “steam engines” of your body. Imagine an enormous cruise ship whose engine isn’t working. It would sit in dry dock and never go anywhere. The most common symptom of mitochondrial myopathy is exercise intolerance. You can have a perfect nutrition plan, eat all the right foods in the right amounts, get enough calories and carbs, take nutritional supplements religiously, get enough sleep and rest, but if you have a breakdown in the electron transport chain and ATP production, you will be stuck in that “dry dock”. In other words, the calories from foods that you consume will not be converted into energy. Nobody wants to be stuck on a cruise ship that is permanently grounded, no matter how grand or magnificent it is!
Let’s expand this discussion of mitochondrial myopathy and exercise intolerance as it relates to exercise physiology specifically. A genetic link in the etiology of mitochondrial myopathy has been identified by researchers as a mutation in the cytochrome b gene, which appears to be somatic, i.e. a spontaneous event that occurs in muscle and does not affect other types of cells. The apparent restriction of these mutations to skeletal muscle is interesting but apparently not unique. A similar restriction has been reported with other mutations of mtDNA that affect both tRNA and protein-coding genes. It has been posited that this relatively rare syndrome has probably been under-diagnosed in the past, due to reports of exercise intolerance as quite common and highly subjective, not to mention problematic to document objectively. Hence exercise intolerance is often dismissed as psychogenic in nature. The finding of lactic acidosis in individuals with exercise intolerance should alert clinicians to the very real possibility of a legitimate cytochrome b gene mutation in an individual. Confirmation of the diagnosis requires muscle biopsy to document a biochemical deficiency and identify the specific molecular defect.
As a whole, exercise intolerance is just as frustrating for clinicians, who frequently have trouble finding a satisfactory diagnosis, as it is for their patients. Numerous studies have now identified cytochrome b gene mutations as a valid mitochondrial etiology underlying exercise intolerance, thus somatic mutations in this mitochondrial gene may be more common than previously believed and may need to be included in the differential diagnosis when patients present with often elusive symptoms such as aches, pain, cramps, and just plain lack of motivation to exercise.
As with most disease states, symptoms of mitochondrial myopathy may be extreme or subtle, but the reality of a mitochondrial defect represents a significant compromise in the quality of life for any person who is limited in their ability to lead a healthy physically active lifestyle. Studies are currently under way to try and develop treatments and pharmacological interventions for those suffering with mitochondrial myopathy. A nutraceutical “cheat” that I have been experimenting with in my own nutrition plan to support my training as a competitive cyclist is a compound known as “quercetin”, admittedly controversial and inconclusive at this point, but studies appear promising. The current literature appears to support quercetin’s efficacy in promoting mitochondrial biogenesis, in regard to both skeletal muscle and other cellular energy pathways, such as the brain and heart.
There is also some intriguing evidence that other nutraceuticals related to mitochondrial biogenesis may be helpful for those of us wishing to optimize our mitochondria, even if we do not suffer from an acute mitochondrial myopathy. These include nicotinamide riboside, creatine monohydrate, alpha-lipoic acid, Co-enzyme Q10, and polyphenols. However, the jury’s still out on whether or not these compounds can promote mitochondrial biogenesis when taken in supra-physiological doses or whether it is simply a matter of an intracellular deficiency of those compounds that diminishes biogenesis and ATP production. For example, we know that ribose is important to the Krebs cycle, but can we conclusively posit that supplementation with D-Ribose powder purchased at our local vitamin shop will definitely boost production of ATP via the electron transport chain? That is unknown at this time. For those of us on the fringe of cutting-edge nutrition science, it always comes down to the laboratory of our own body, the biohacker’s classic N = 1 experiment. If you’re low on energy and unmotivated to exercise, talk to your doctor about getting tested for mitochondrial myopathy and try some of the nutraceutical hacks that I discussed in this article. If you have tried something that works for you, please leave a comment on this blog. I always welcome feedback from my followers!