Long COVID presents with a myriad of potentially disabling symptoms from cognitive to musculoskeletal. The fatigue and pain in fibromyalgia also prevent ADLs. The clinical challenge in treating these patients is to restore normal physiology, regain homeostasis and rebuild energy levels. This is where mitochondria, the powerpack of every cell, play a role.
The novel coronavirus SARS-CoV-2, has precipitated an unprecedented global health crisis, the repercussions of which continue to resonate worldwide. While a significant proportion of those infected with COVID-19 recover, a startling observation has emerged: more than 70% of survivors experience lingering symptoms 4 months post-infection, giving rise to what is now recognized as Long COVID Syndrome. (Molnar 2024)
Current statistics show that chronic fatigue is the most frequently reported symptom of long COVID, with dyspnea, arthralgia, sleep disturbances, mood disorders, depression, headaches, dizziness, cardiac symptoms and cognitive impairments (brain fog) also documented. The severity spans a wide range, from being annoying to preventing simple self-care. When a patient presents with a condition that you routinely treat and the response is slow or refractory, consider long COVID as a co-morbidity.
Mitochondrial Dysfunction
Mitochondria are essential for cellular energy via oxidative phosphorylation, maintaining cellular and systemic homeostasis. Every cell (except RBCs, which contain no organelles) depend on mitochondria to manage oxidative stress, apoptosis (programmed cell death), induction of cellular senescence, and the modulation of immune responses. However, mitochondrial dysfunction reduces energy output, increases inflammation and diminishes cellular respiration, making it a key player in health and disease.
Clinical Tip: Mitochondrial dysfunction in the brain may present as Alzheimer’s, cognitive impairment or brain fog: in the pancreas, blood sugar issues, as in type 2 diabetes, may be seen: in the intestines, leaky gut or irritable bowel disease arises. Even cancer has been linked to mitochondrial dysfunction.
Post-Viral Fatigue Syndrome
Post-viral fatigue syndrome (PVFS) is characterized by overwhelming fatigue and widespread musculoskeletal pain not alleviated by rest and that cannot be explained by an underlying medical condition. In addition to fatigue and chronic pain, patients also present with post-exertional malaise, unrefreshing sleep, cognitive impairments, orthostatic intolerance, and GI complaints.
The etiology of PVFS is multifactorial, may develop suddenly or insidiously, and is typically associated with triggering events such as viral infections, physical and/or emotional trauma.
Traditionally, PVFS encompassed myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and fibromyalgia (FM); it now includes long COVID.
Making the Connection
As with long COVID, there is an established link between mitochondrial dysfunction and ME/CFS and FM. Similarly, the chronicity and severity of symptoms in ME/CFS and FM have been related to decreased ATP production, impaired mitochondrial respiration, abnormal mitochondrial DNA levels, immune dysregulation, increased oxidative stress, imbalanced redox metabolism, and chronic systemic inflammation.
Biomarkers of mitochondrial dysfunction, such as markers of oxidative stress and mitochondrial DNA damage, may aid in the diagnosis and subtyping of PVFS; however, this has not been established. Outcome assessment tools and a trial of care aimed to increase mitochondrial function through lifestyle, nutrition, and exercise is an appropriate course of treatment for these conditions; essentially, a multimodal chiropractic treatment plan.
Clinical Tip: FM patients have depleted CoQ10 levels (typically 40–50% lower). CoQ10 (alone or in nutrient combinations) has been shown to be effective for symptomatic relief of FM. In a randomized, controlled trial of ME/CFS patients, a dose of 200 mg of CoQ10 and 20 mg of NADH per day for three months demonstrated significant improvement in fatigue perception. Mantle recommends a crystalline form of ubiquinol with selenium for optimal absorption.
A Treatment Roadmap
Obviously mitochondrial dysfunction is a significant issue in long COVID and in PVFS. While a detailed review of the nutritional supplements that increase mitochondria respiration is beyond the scope of this article, there are nutritional guidelines that can be generalized.
Diet / Supplements
First, reduce systemic low-grade inflammation with diet. Next, consider nutritional support for the dysfunctional tissue stacked with additional antioxidants that have been shown to assist in mitochondrial function.
The anti-inflammatory diet is a start for lifestyle change. Dr. David Seaman has promoted an anti-inflammatory diet for decades and the details can be found online. Hit it hard, no cheating. Add to that known antioxidants that stimulate mitochondrial function, such as alphalipoic acid, vitamin C, resveratrol and quercetin. Then for an extra anti-inflammatory punch, add omega-3s, boswellia, turmeric and ginger.
Clinical Tip: Read your supplement labels closely. Look for binders, fillers, food colorings, excipients, and ask about sourcing and quality control. Make sure what is on the label is in the bottle, so ask for independent quality assays. When recommending herbal formulas, be sure they are standardized so every batch has the same concentration.
Exercise / Training
In addition to diet and supplements, we can take information gained from training athletes to perform better and recover faster. For athletes, energy production is focused on increasing ATP production, oxygen utilization (VO2max), and recovery – principles that can be applied to the deconditioned and dis-eased patient.
San-Millán contends: “It has been known for decades that physical activity is probably the only known intervention that can improve mitochondrial function. However, an individualized exercise prescription should be crucial for the ‘metabolic rehabilitation’ of many patients.”
Since daily life is an endurance event, San-Millán extrapolates the techniques used for training elite-level endurance athletes into the general population; specifically, training below anerobic threshold for 40+ minutes daily. Obviously this is the goal and not the starting point for a patient with long COVID or PVFS, but we can track simple biomarkers such as heart rate, relative perceived exertion and aerobic capacity as we build our patients up.
Since the 1960s, we have known the benefits of endurance training for mitochondrial function. Twelve weeks of endurance training (five days/week) can increase mitochondrial enzymes twofold. (Hollozsy). One hour of cycling for four days/week over five months at an intensity of 70-90% of the VO2max increases the oxidative and glycolytic capacity by 95 and 117%, respectively (Gollnick).
Skeletal muscle is the largest organ in the body, so by increasing skeletal muscle, mitochondrial function energy increases via increased ATP, oxidative stress is reduced and the immune response is improved, leading to a systemic return to homeostasis.
Oxygen transport and delivery into the tissues is closely monitored in elite athletes with VO2max and lactate threshold testing. An easy in-office test for oxygen transport capacity is the BOLT test, which is a measurement of the time it takes for your body to react to a lack of air, a biomarker of oxygen utilization. Here are the steps to a BOLT test:
- Take a normal breath in through your nose and allow a normal breath out through your nose.
- Hold your nose with your fingers to prevent air from entering your lungs.
- Time the number of seconds until you feel the first definite desire to breathe, or the first stresses of your body urging you to breathe.
- Release your nose and breathe in through your nose. Your inhalation should be calm.
- Resume normal breathing.
A normal BOLT score is approximately 20 seconds; less than 10 seconds is poor and over 40 seconds is excellent. Your BOLT score can be improved with breathing exercises. Mitochondria like oxygen.
Clinical Takeaway
Mitochondrial dysfunction is related to more than long COVID and PVFS; it is related to any disease produced by inflammation and poor cellular respiration such as type 2 diabetes, cardiovascular disease, metabolic syndrome, cancer, and Alzheimer’s disease.
Currently, the best option to improve mitochondrial function and restore homeostasis is via a multimodal approach of nutrition, supplements and aerobic endurance training. Adding in chiropractic adjustments to keep our patients physically capable of exercising and as a neurological reboot will accelerate the response.
Resources
- Gollnick PD, et al. Effect of training on enzyme activity and fiber composition of human skeletal muscle. J Appl Physiol, 1973;34:107-111.
- Holloszy JO. Biochemical adaptations in muscle. Effects of exercise on mitochondrial oxygen uptake and respiratory enzyme activity in skeletal muscle. J Biol Chem, 1967;242:2278-2282.
- Mantle D, et al. Mitochondrial dysfunction and coenzyme Q10 supplementation in post-viral fatigue syndrome: an overview. Int J Mol Sci, 2024:25:574.
- Molnar T, et al. Mitochondrial dysfunction in long COVID: mechanisms, consequences, and potential therapeutic approaches. GeroScience, 2024;46:5267-5286.
- San-Millán I. The key role of mitochondrial function in health and disease. Antioxidants, 2023;12:782.
