Masters of Health Magazine January 2024 | Page 28

Much of this mitochondrial research has focused on defects in the electron transport chain (ETC) embedded in the membranes of the mitochondria. The ETC directly fuels the ATP synthase enzyme vital to the production of ATP at the end of that chain. The ETC has four main complexes, or steps, that work to optimally shuttle electrons to the terminal ATP-producing enzyme. [118,119] These complexes and their significant characteristics can be summarized and simplified as follows:

•         Complex I: NAD (nicotinamide adenine dinucleotide) in its reduced form, NADH, starts the electron donation sequence.

•         Complex II: FAD (flavin adenine dinucleotide) in its reduced form, FADH2, continues the electron relay to ubiquinone (oxidized coenzyme Q10 [CoQ10]).

•         Complex III: Ubiquinol (reduced CoQ10) relays the electrons to cytochrome c.

•         Complex IV: Cytochrome c oxidase then receives the electrons where molecular oxygen is bound and reduced to water.

•         ATP synthase (also known as complex V) is then activated to complete the ETC electron shuttling with the subsequent production of ATP.

 

Mitochondrial dysfunction is most successfully addressed when the substrates of the ETC (NAD, FAD, CoQ10) are either directly supplemented or the precursors needed for their synthesis are supplemented. Fueling the ETC not only produces more ATP, it also results in less oxidative stress being generated in the process by the ETC agents as mitochondrial function becomes more efficient and total cellular oxidation declines. [120,121] And when ATP can be increased and oxidative stress can be decreased, mitochondrial healing can take place. Such healing is suggested in a study that found cardiovascular mortality to remain reduced for eight years following the completion of a four-year period of supplementation with CoQ10 and selenium. [122]

Defects in the ETC have been specifically identified in heart failure and are always present. [123] In even the most advanced cases of heart failure, most affected hearts still have inflamed but viable heart cells that can be positively impacted with improved ATP production. Aside from the chelation therapies noted above, bolstering mitochondrial function has been a major physiological goal in the treatment of heart failure. [124] While heart disease can occur from inherited mitochondrial disorders, most cases of heart failure are due to diseased mitochondria because of the pathogens and accumulated toxins in the heart. [125]

Traditional medicine has no drugs which directly work to normalize mitochondrial dysfunction in heart failure patients. Instead, all the current prescription drugs work only to basically mobilize excess fluid accumulations and/or to lessen the workload (peripheral resistance) faced by the failing heart muscle. This is not to say that there is no place for these drugs, only that they should not be the only agents given to the patient. As with most prescription drugs, the therapeutic goal appears limited to symptom improvement while letting the underlying pathology continue to evolve. Traditional medicine is much better at diagnosing and naming medical conditions than at reversing or resolving them.

When targeted therapies capable of entering the ETC of the mitochondria and improving ATP production are utilized, the clinical response in heart failure is often dramatic. These include many of the patients considered to have terminal congestive cardiomyopathies and no possibility of improvement or significant long-term survival without heart transplantation.

CoQ10 is the most researched of these ETC-targeted therapies for cardiomyopathy, and its enormous benefits on cardiac function have been well-documented. The especially vital role of CoQ10 in supporting ATP production in the heart is reflected in its concentrations in different tissues in the body. Far more CoQ10 is found in the heart than is found in any of 12 other human tissues examined. Furthermore, the heart contained roughly twice as much CoQ10 as the kidneys, the organ/tissue in the study with the second highest CoQ10 concentrations. Non-cardiac muscle had only one-third of the CoQ10 as the heart muscle. [126]

CoQ10 directly promotes the mitochondrial ETC by supporting the electron transfer in complexes I and II, as well as by its established role in complex III. Its impact in restoring heart function in cardiomyopathy has been significant and sometimes stunning, especially since this is a condition that is only given supportive care by traditional cardiologists while steady cardiac deterioration continues.

In a randomized, double-blind trial in 420 patients with severe heart failure and followed for two years, there was a 42% reduction in all-cause mortality and cardiac mortality in patients given 100 mg of CoQ10 three times daily. Fewer hospitalizations for heart failure occurred in the treated group as well. [127] The supplementation of selenium along with CoQ10 appears to be especially effective in reducing mortality in cardiomyopathy patients. [128]

The ejection fraction (EF), a measure of how effectively the heart contracts and empties on each beat, is the most direct objective and readily measurable parameter to evaluate cardiac function. EFs considered to be normal run roughly from 65 to 80%. EFs of 10% to 15% represent the greatest loss of cardiac function and are characteristic numbers for patients on heart transplant waiting lists. CoQ10 supplementation has rescued many patients considered to have terminal heart failure, and this has been accompanied by dramatic improvements in EF and functional capacity in most patients, with one study showing the mean EF going from 25 to 42%. [129-134] It should also be noted that increasing an EF from 15% to 25% can take a patient who has difficulty walking across the room without shortness of breath to one who can function normally as long as major physical stresses are avoided.

The initial pathology seen in the heart failure of hypertrophic cardiomyopathy with preserved EFs is also clearly improved with CoQ10 supplementation. [135,136]

Low CoQ10 levels, along with increased CRP (C-reactive protein, a marker of oxidative stress) levels have been documented in heart failure, whether due to coronary disease or of unknown cause. [137] Other studies have also shown that lower CoQ10 serum levels correlated with increased all-cause mortality in general, as well as in heart failure patients. [138,139]

Conversely, CoQ10 supplementation has been shown to decrease all-cause mortality in all subjects. Furthermore, the CoQ10 supplementation clearly increased exercise capacity in the heart failure patients while having no significant adverse effects or safety issues. [140-143] First discovered in 1955, the benefits of CoQ10 in heart failure have been documented extensively in the scientific literature for 50 years now, yet the established textbooks of medicine and medical therapeutic manuals make no mention at all about this vital nutrient antioxidant, much less its impact on congestive heart failure. [144-148]

As CoQ10 increases the energy production in all the cells in the body, it should not be surprising that studies have shown its benefits in a wide variety of diseases. Low levels have been documented in many medical conditions, along with evidence of its clear benefits when properly supplemented or administered. Such conditions include the following: