Mitochondrial Dysfunction: A Critical Component in Managing Myalgic Encephalitis/Chronic Fatigue Syndrome


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Treatment Goals

Treating mitochondrial dysfunction is a multi-tiered approach.  The first step is trying to repair the mitochondrial membrane, which is made up of primarily phospholipids. These phospholipids consist of phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol (PI), phosphatidylserine (PS), and phosphatidic acid (PA), as well as phosphatidylglycerol (PG) and cardiolipin (CL).27  Phosphatidylglycerol and cardiolipin are unique to mitochondrial membranes where the other phospholipids are present in all cell membranes.27  Reactive oxygen species oxidize the mitochondrial membrane phospholipids, which damages the membrane integrity.28  When cardiolipin is released, it causes the release of cytochrome c leading to apoptosis of the mitochondria.28   Damaged mitochondrial membranes cause a proton leak, leading to a decrease in ATP production.28

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Supporting the nutrients critical for mitochondrial function is the next step in treating dysfunctional mitochondria.  Nutrients can be low from poor dietary intake, aging, and increased metabolic needs. Levels of CoQ10, carnitine, and NADH needed for mitochondrial function tend to decrease with aging and chronic disease. Decreased levels of both CoQ10 and carnitine have been associated with mitochondrial dysfunction in ME/CFS.19,20 Therefore these two nutrients are critical for mitochondrial support.  Pyrroloquinoline quinone (PQQ) is a nutrient that  is involved in cell signaling pathways that impact mitochondrial energy metabolism and neurologic functions.29 Supplementing with PQQ in human subjects showed a decrease in inflammatory markers and an improvement in mitochondrial markers.29  NAD/NADH are involved in energy metabolism and mitochondrial function and therefore are other critical cofactors for mitochondrial support.30 Many of the B vitamins are cofactors for the enzymes of the Krebs cycle, which precedes the electron transport chain and the formation of ATP.

Antioxidants are also critical nutrients needed to counteract mitochondrial dysfunction.  Oxidative stress plays a key role in contributing to mitochondrial damage of the membrane, DNA, and proteins.28 Multiple antioxidants contribute to removing excess free radicals from the mitochondria.  Vitamin C enters the mitochondria to protect it from oxidative injury.31  The combination of alpha-lipoic acid (ALA) and vitamin E supplementation improved ATP levels in animal studies in the liver, heart, kidney and brain along with significant improvements in the electron transport complex I activity.32


ATP360

ATP360 is a supplement designed to encompass complete mitochondrial support with mitochondrial membrane repair, mitochondrial nutrients, and antioxidants.  The nutrients in the supplement were picked based on research in supporting mitochondria.  Research on the entire product showed improvement in clinical symptoms, laboratory markers, and mitochondria function.

An open label study design was used for investigating ATP360.33 Patients with moderate- to long-term fatigue scoring higher than 50% on the Piper fatigue scale were entered into the study.  The participants consumed ATP360 for eight weeks with evaluations at 1, 4, and 8 weeks.  Additional healthy participants matching the study participants donated blood for comparison of the mitochondria.

The results showed a reduction in long-term fatigue beginning after one week of use.  Additional changes in quality of life were seen, including improvements in pain, mental functioning, sleep, energy, and emotional wellness. Indicators of inflammation such as levels of TNF-alpha, IL-8 and elevations of diastolic blood pressure were reduced.  When the mitochondria were tested, the fatigued participants had lower mitochondrial function when induced by inflammation compared to the health participants. With four weeks of supplementing with ATP360, the mitochondrial function of the fatigued participants showed improvement.


Summary

ME/CFS causes significant morbidity and a decrease in quality of life for many people.  Understanding how the mitochondria, which supply cellular energy to the body, are negatively impacted in ME/CFS is a step forward in understanding and treating the disease.  Mitochondrial dysfunction can be identified and treated with targeted nutrients that address membrane repair, supply critical cofactors and antioxidants, and can be a strong step in helping improve symptoms and quality of life for people with ME/CFS.


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