FOR IMMEDIATE RELEASE
Orthomolecular Medicine News Service, November 3, 2023

Heart Failure or Therapy Failure?
Toxins Cause Cardiomyopathy

Thomas E. Levy, MD, JD, Contributing Editor

OMNS (November 3, 2023) Cardiomyopathy simply means heart muscle disease. [1] It can occur as a primary affliction of the heart muscle, from a secondary condition negatively impacting heart function, or from a combination of both these clinical conditions. [2,3] Relatively recent changes in the definition of cardiomyopathy have been put forward that differ somewhat with these long-standing categorizations of heart disease. However, for the practicing clinician, the most important considerations in approaching the cardiomyopathy patient with clinical heart failure are:

• Is the heart muscle itself diseased?
• Is the heart muscle normal but being forced into failure by non-cardiac factors?
• Is the clinical presentation a combination of both these conditions?
• Is the treatment protocol aimed only at relieving symptoms or also at resolving the underlying pathology resulting in the clinical heart failure?

Because cardiomyopathy presenting as clinical heart failure is a condition typically involving multiple factors, there is no single clinical protocol that can be considered the optimal treatment plan. Furthermore, heart failure rarely occurs by itself without other diseases and co-morbid conditions being present and contributing to symptoms as well. [4,5] However, all presentations of heart failure share features that should always be addressed clinically, regardless of whatever other treatments are being administered. The huge public health impact of heart failure cannot be overstated. In Germany, for example, heart failure is the most common primary inpatient diagnosis. [6]

Heart Failure Pathophysiology

When the function of the heart is impaired sufficiently to decrease the amount of blood that should be pumped with every heartbeat (cardiac output), a clinical picture of heart failure will eventually emerge. As the body can clinically compensate reasonably well for early heart failure, it is only when the decreased function is severe enough and chronic enough that heart failure symptoms become clear-cut. Because of this, even seemingly mild heart failure symptoms should be taken very seriously, with a complete diagnosis (especially in the ongoing pandemic setting), and the application of scientifically-based treatments for supporting and improving heart function.

Common symptoms of heart failure include the following, due basically to the abnormal accumulation of fluid in the lungs and the rest of the body from inadequate heart pumping ability: [7,8]

• Shortness of breath at rest or too quickly with exertion
• Shortness of breath when lying flat
• Waking up suddenly short of breath
• Fatigue
• Swelling in feet, ankles, and eventually legs and/or abdomen
• Accelerated heart rate, palpitations

Heart muscle cells do not just fail and "wear out" for no reason. When oxidative stress increases inside the heart tissue, inflammation by definition then exists as well. Also, part of that increased oxidative stress is the result of decreased ATP (adenosine triphosphate) production in the mitochondria of the heart cells. As ATP is the main energy-providing molecule in the body, those heart cells that have compromised ATP production have more oxidative stress, which results in a clinical picture of inflammation, or myocarditis.

When the factors increasing oxidative stress are intense and acute in onset, rapid heart enlargement with poor heart contraction (congestive cardiomyopathy) will result. However, when the factors increasing oxidative stress are less intense and more chronic in nature, the heart will generally first "adapt" by increasing the heart wall thickness without enlargement of the left ventricular dimensions (hypertrophic cardiomyopathy). A clinical picture of heart failure will still be present and continue to evolve as the heart wall thickening makes the left ventricle stiffer and less compliant. This results in that heart chamber not filling up as readily (diastolic heart failure, or heart failure with preserved ejection fraction). [9,10] Effectively, this form of cardiomyopathy actually consumes more ATP trying to fill the heart than to empty it. [11]

With this resistance to chamber filling, the amount of blood pumped with each heartbeat decreases while the blood supply coming into that chamber "backs up," resulting in the heart failure symptoms noted above. To be discussed below, toxins cause both forms of cardiomyopathy. Left untreated, the terminal stages of hypertrophic cardiomyopathy evolve into a congestive cardiomyopathy, with substantial enlargement of the left ventricle and very poor contractility. This will result even when the heart was not enlarged or poorly contracting at the onset of the myocardial inflammation. The initial clinical presentation of heart failure is roughly split equally between hypertrophic and congestive cardiomyopathy. [12]

Limited blood flow in the heart (ischemia) is commonly considered to be the cause of congestive cardiomyopathy most of the time. This is certainly a major reason for heart failure when multiple heart attacks with death of heart muscle and fibrotic scarring are present in place of contracting heart muscle. However, heart biopsies in consecutive patients with advanced coronary artery blockages and clinical heart failure indicated otherwise. The microscopic evaluation of these biopsies indicated that myocarditis was the underlying cause, and heart function in some of these patients improved dramatically with anti-inflammatory measures. In the absence of active ischemia or old heart attacks with extensive loss of heart tissue, it is erroneous to consider ischemia as a primary cause of congestive heart failure. The important takeaway point is that myocarditis is not necessarily an obvious diagnosis. There must be a lower threshold for taking heart tissue biopsies, as missing the diagnosis of a treatable condition greatly increases morbidity and mortality for many patients. [13]

Toxins and the Heart

While toxin accumulation in the heart muscle can be the singular cause of advanced heart failure, it will much more often be one of several factors contributing to decreased heart contractility. Also, the chronicity of the heart failure, regardless of cause, will play a large role in determining its reversibility, as more and more inflamed heart cells will eventually die and not just remain in a chronically inflamed state. Such inflammation is consistently seen on the microscopic study of heart biopsies in toxin- and infection-related cardiomyopathy. [14,15] Many different toxins, including many heavy metals, have been either linked to heart failure or clearly shown to be the direct cause. Furthermore, one or more of these toxins is nearly always present in high concentrations in the affected heart muscle. A partial list of such agents includes the following:

• Lead
• Copper
• Iron
• Mercury
• Aluminum
• Cobalt/Chromium
• Cadmium
• Gold/Silver
• Chemotherapy
• COVID Spike protein

Lead: In a 3-year-old girl with chronic lead poisoning, acute heart failure developed that was clinically reversed after four days of calcium EDTA chelation therapy. [16] Children who died from heart failure secondary to acute lead poisoning were documented to have the microscopic findings of myocarditis. [17] Lead has been shown in other studies to target the heart and the vascular system. [18-21] Animal studies have also shown that enough lead exposure will reliably cause myocarditis and vascular damage as is seen in humans. These studies show that lead exposure will cause atherosclerosis and high blood pressure as well. [22-24]

Copper: A transition metal necessary for normal cell function but easily pushed to excess and toxic levels in the body, copper is another culprit toxin commonly involved in cardiomyopathy patients. [25,26] Excess copper appears to be especially toxic to the heart, as the infusion of copper into the coronary circulation of rats results in impaired heart function in only minutes. [27] Hypertrophic cardiomyopathy has been strongly linked to the excess copper levels seen in Wilson's disease. Trientine, a selective chelator of copper, has been shown to improve cardiac function in hypertrophic cardiomyopathy patients. [28]

In a randomized, placebo-controlled trial on diabetic patients with left ventricular thickening (that can lead to hypertrophic cardiomyopathy), copper chelation significantly decreased the heart wall thickening. This study did not even screen for elevated copper levels. [29,30] Furthermore, trientine chelation in diabetic rats with advanced left ventricular failure over an eight-week period demonstrated significantly improved heart function. [31] Another heavy metal-removal study in diabetic rats with either trientine or citrate (citric acid) significantly protected heart function. [32] In a case report a patient with scleroderma and a congestive cardiomyopathy improved dramatically on penicillamine, an effective chelator of copper, lead, and mercury. No copper level testing was reported as part of the evaluation of this patient. [33] These studies further indicate that toxicity from copper and/or other heavy metals in the heart is often a significant contributing factor in patients with early heart wall thickening and then its later decompensation into decreased cardiac function and heart failure.

It appears that a clear diagnosis of copper excess does not need to be made before just treating patients presumptively as having too much copper in their heart, especially when heart wall thickening is present in a diabetic patient. [34] It has also been shown a copper-overload state is a primary factor in the pathogenesis of damage to any organ in the diabetic. [35] Copper removal has also been shown to decrease the inflammatory response to radiofrequency ablation treatment for liver cancer in rats. [36] These findings strongly suggest that:

The unsuspected presence of excess copper in tissues and organs can impair the resolution of ANY pathology being treated, indicating a positive role for copper removal for nearly all medical conditions.

Iron: Congestive heart failure secondary to severe iron overload in the body has been described. The daily administration of an iron chelator (deferoxamine) in a congestive cardiomyopathy patient over roughly a year dramatically improved heart function and cardiac output, with heart pumping ability more than doubling (ejection fraction from 20% to 48%). [37] Another case report described a 27-year-old woman with "severe heart failure" completely normalizing on an iron removal regimen. [38] Patients with severe iron overload cardiomyopathy have an average survival of only one year when therapeutic phlebotomy (blood donation) and iron chelation are not utilized. This form of cardiomyopathy begins with restricted filling of the heart (diastolic dysfunction), and then evolving into a congestive cardiomyopathy. [39]

Iron overload cardiomyopathy occurs most commonly in patients with hereditary hemochromatosis or secondary hemochromatosis (as with β-thalassemia and sickle cell anemia). [40] However, excess iron short of that seen in full-blown hemochromatosis can still be expected to inflict its own dose-dependent toxicity. Most adults already have excess levels of iron in their bodies, as reflected by elevated ferritin levels that erroneously remain regarded as normal in laboratory reference ranges. [25] Excess iron in the heart is also a predisposing factor to developing atrial fibrillation, an arrhythmia that contributes its own increased morbidity and mortality. [41]

In animal studies, excess cellular iron in heart cells has been shown to increase oxidative stress and impair the ability of the mitochondrial electron transport chain (ETC) to produce ATP. As ATP is the primary energy-providing molecule in the body, any decrease in its production always results in compromised cellular function and disease. [42,43] Of note, resveratrol supplementation has been shown to dramatically improve heart function in animal models of iron overload cardiomyopathy. [44-46] In another animal study, either deferiprone or N-acetylcysteine was effective in decreasing cardiac iron concentration. [47]

Mercury: As the most toxic non-radioactive element, mercury is a heavy metal that causes grave damage wherever it accumulates. A landmark study directly compared toxic heavy metal concentrations in biopsies of heart muscle against control muscle biopsies in patients with idiopathic dilated cardiomyopathy (IDCM), meaning advanced heart failure of unknown cause. The cardiomyopathy heart muscle had 22,000 times more mercury in it than in normal heart muscle. Versus normal specimens, the same diseased heart muscle had 12,000 times more antimony, 11 times more gold, 13 times more chromium and 4 times more cobalt. Of great significance, there was no primary screening to detect increased heavy metal exposure in the study group, meaning these accumulations likely represent the finding in most cases of IDCM. [48] Unless excess exposures to heavy metals are readily apparent, the widespread effects of such poisonings make it very unlikely that such a toxicity will be suspected and then correctly diagnosed. [49]

In another study, the heart muscle in cardiomyopathy patients examined at autopsy revealed significantly higher levels of lead, nickel, copper, and manganese, and significantly lower levels of zinc compared to the heart muscle in non-cardiomyopathy patients. Mercury and antimony levels were not reported and presumably had not been measured. [50] This study indicates that most patients with IDCM have not only astronomical levels of mercury and antimony, but also significant elevations of lead, nickel, and copper. If it was not a vital organ, the ability of the heart to selectively remove heavy metals out of the blood and the rest of the body could be considered a protective mechanism for the health of the body! This leads to the conclusion that:

Cardiac muscle in patients with advanced congestive cardiomyopathy is the preferred collection site for most of the heavy metals taken into the body.

Currently, IDCM is the cause of heart failure in over 100,000 people in the United States, and it is the underlying diagnosis leading to 45% of heart transplants. Furthermore, evidence of resolved or ongoing viral infection in heart biopsy specimens are seen in 25% of IDCM patients. [51] Up to 80% of IDCM patients demonstrate one or more anti-heart autoantibodies. [52] Such antibodies are commonly the result of occult infections. Heavy metal accumulations and chronic viral myocarditis appear to be pathology-precipitating partners. [53] While it is unclear whether one factor better facilitates the presence of the other, it appears that heavy metal accumulation, headed by mercury, is a very common cause of IDCM. Based on these studies that have specifically measured heavy metal status in IDCM heart muscle, heavy metal accumulation appears to be the culprit for this advanced form of heart failure MOST of the time. The IDCM heart would appear to be a chemically attractive site for the accumulation of multiple heavy metals after being primed by an earlier myocarditis-precipitating viral infection, as no other organ in the bodies of IDCM patients appears to similarly concentrate these toxins.

Mercury also works effectively to produce a deficiency state of selenium. Restoring deficient selenium stores can lessen clinical mercury toxicity, although it does not directly promote the mobilization or elimination of mercury. Congestive cardiomyopathy secondary to selenium deficiency has been reported, and restoring depleted selenium levels can reverse it. [54-57] Based on the data above on mercury and IDCM, a cardiomyopathy associated with selenium deficiency is likely a cardiomyopathy due to the toxicity of excess mercury no longer being negated by a sufficient presence of selenium. Of note, too much supplemental selenium has its own toxicity, unlike many other nutrient supplements, and should not be overdone.

Aluminum: Aluminum phosphide, an agent used as a pesticide, induced a severe, but reversible, cardiomyopathy after accidental poisoning in an exterminator. [58] Intense supportive care to reverse low blood pressure was shown to facilitate the recovery of other individuals poisoned with aluminum phosphide that resulted in severe compromise of heart contractility. [59,60] In a hemodialysis patient who expired with heart failure, heavy aluminum deposits were seen in the heart cells upon electron microscope examination. [61] An animal study also showed that aluminum chloride could induce a largely reversible cardiomyopathy. [62] Organic acids (succinic, malic, or citric) and the iron chelator, desferrioxamine, are agents that can mobilize (solubilize) and eliminate aluminum accumulations. [63]

Cobalt/Chromium: Cobalt is another toxic heavy metal documented as a cause of congestive cardiomyopathy. Elevated blood cobalt levels have been identified in some metal hip implant patients. [64,65] Elevated blood chromium levels from the implants can be seen as well. [66,67] However, the presence of such elevations is not an assurance that a cardiomyopathy will result. [68] As noted above, IDCM often starts with an undiagnosed viral myocarditis. Such a myocarditis would appear to inflict the myocardial damage that triggers the almost sponge-like uptake of cobalt and other heavy metals, as described in the section on mercury accumulation in the heart. An animal study also showed that poor diet (protein restriction) further predisposed the heart to cobalt toxicity. [69] N-acetylcysteine is effective in significantly reducing the blood concentrations of both cobalt and chromium. [70] Alpha lipoic acid is another effective chelator of cobalt. [71]

Cadmium: A study examining blood, serum, and urine heavy metal levels found significantly higher cadmium levels in IDCM patients than in healthy controls. [72]

Gold/Silver: While gold and silver are not recognized as toxic substances in general, some care always needs to be exerted in a supplementation regimen, especially one involving metals. In a case report, a dilated congestive cardiomyopathy resulted from the excessive ingestion of colloidal gold for about three months, along with a history of intermittent colloidal silver ingestion over the prior seven years. In addition to an enlarged heart that was contracting poorly, a significant new heart conduction abnormality (left bundle branch block) resulted from this supplementation. Following chelation therapy (dimercaprol) the block disappeared and the ejection fraction of the heart improved from 20% to 50%, a very dramatic improvement. Of note, urine screening (no tissue levels measured) revealed no evidence of excess aluminum, arsenic, barium, beryllium, cadmium, copper, manganese, or thallium. [73]

Chemotherapy: Cancer chemotherapy utilizes some agents that are highly toxic to the heart. Anthracyclines (doxorubicin, idarubicin, epirubicin, mitoxantrone) often result in some heart enlargement and decreased contractility. [74,75] These are cardiac effects that are still considered to be largely irreversible, even though chelation therapy has been shown to be effective in preventing such cardiac damage. [76-79] Considering that multiple toxins and heavy metals are typically present in patients with IDCM, it should not be assumed that trying to remove as much of the toxin load from the body (and the heart) will be of no benefit. Cancer patients typically have other diseases as well, and it is reasonable to think that some of these patients (such as those with the copper accumulation often seen in diabetes) might have already been accumulating cardiac toxins before there was any evidence of cardiac compromise. As such, chelation therapy would have the potential to at least partially reverse the cardiac damage currently seen with chemotherapy.

COVID Spike Protein: Persistent spike protein (PSP) syndrome is seen when the COVID pathogen-related spike protein stays in the body following a COVID vaccination and/or because it was never completely eliminated following an unresolved COVID infection (chronic or long-haul COVID). [80-82] While the spike protein has been found throughout the body in autopsy studies on COVID patients, it appears to have a particular predilection for attacking the heart and its blood vessels. [83-88]

The spike protein inflicts damage in the heart and elsewhere in the body by multiple mechanisms. These mechanisms include:

• Facilitating COVID pathogen entry into cells (ACE2 receptor binding). [89-91]
• Overstimulation of the immune response by being chronically present, evolving into an autoimmune disease. [92-94]
• Attacking not only tissue and organ cells directly, but also the walls of the blood vessels and the platelets circulating in them, resulting in the increased formation of blood clots. [95,96]
• Intrinsic toxicity of both the complete spike protein as well as fragments of it. [97-99]
• The ability to enter the genome of the cell where it currently cannot reliably be eradicated, along with the seeming ability to be replicated indefinitely. [100]

Myocarditis, often evolving heart enlargement and heart failure, can result from the spike protein exposure following COVID vaccine(s) and/or from its persistence presence in chronic COVID. However, many cases of spike protein myocarditis, probably a substantial majority, are chronic, smoldering conditions that remain undiagnosed except when there is clear clinical evidence indicating its presence.

PSP syndrome routinely involves the heart, even when not readily apparent clinically. In fact, the spike protein has such a preference for heart muscle that chronic COVID or post-vaccination patients are unlikely to ever have spike protein or its pathological impact elsewhere in the body while sparing the heart. In autopsies of patients who died of COVID-19, either COVID-related viral RNA or evidence of myocardial inflammation was seen more than 80% of the time. [101] Another autopsy study revealed spike protein presence over 60% of the time. [102]

Clinically significant myocarditis secondary to PSP can often be missed and completely unsuspected clinically due to the patchy and limited nature of many cases of spike protein myocarditis. [103] In a case report, conduction system cells (AV node) of the heart were selectively inflamed, suggesting why even a minimal, undetected spike protein myocarditis can trigger lethal arrhythmias. [104] In another case report autopsy, the spike protein in the heart was most dominant in the AV node as well as in the pacemaker cells in the atrium. Scattered throughout the heart were single necrotic (dead) heart cells, adjacent to viable cells. [105] Another autopsy study also reported this single-cell death in COVID hearts. [106,107]

Unlike the other toxic cardiomyopathies, spike protein only rarely involves the whole heart, and the amount of heart muscle involvement can be very minimal. Nevertheless, sudden cardiac death (not from a heart attack due to "traditional" coronary atherosclerosis) is no longer uncommon, and it appears a substantial number of individuals around the world can be symptom-free and still be liable to life-threatening arrhythmias under conditions of stress, including previously-healthy young athletes. [108]

As the number of people with undetected spike protein/COVID myocarditis is enormous already and steadily increasing, part of the therapy for anyone felt to have persistent spike protein should still involve the regular administration of one or more heavy metal chelation agents. As discussed above, heavy metals appear to "await" the microenvironment of myocardial inflammation of a previous viral infection to begin accumulating, if they have not already accumulated there prior to the COVID infection or the vaccine administration. As with all other toxins, heavy metals will always substantially worsen any inflammation and electrical instability already caused by the presence of the spike protein and the COVID pathogen. Most likely this worsening is synergistic in nature, and not just the additive effect of spike protein and heavy metals.

Before the diagnosis of idiopathic (unknown origin) cardiomyopathy is made, toxic and infectious causes must be ruled out. If the absence of these causes is not clearly established, prophylactic nutrient chelation should always be part of any therapeutic protocol, or the reversibility of clinical heart failure will never be realized. Currently, such diagnostic effects are rarely made. [109]

ATP Physiology and Cardiomyopathy

No cell, whether in the heart or elsewhere, is healthy when mitochondrial function and ATP production are chronically suppressed. Such suppression will reliably occur when the reduction-oxidation balance inside the cells is sufficiently shifted toward excess oxidation. All diseased cells have too little antioxidant presence, and this is reflected in higher cellular levels of calcium and lower cellular levels of magnesium, vitamin C, and glutathione. When these levels remain abnormal, mitochondrial ATP production will always be depressed as well. These cellular abnormalities are always present in diseased tissues or organs. [110,111]

When cardiac ATP production can be restored to optimal levels with a normal increase capability for exercise, a healthy heart will result, unless irreversible damage has already taken place. [112] Of note, mitochondria are especially abundant in heart tissue, and more than 90% of the energy of the heart is generated by these mitochondria. As the heart completely renews its ATP content every 20 seconds or so, it can demonstrate clear mitochondrial insufficiency (heart failure) when other organs appear to be less affected or completely unaffected. [113,114] No organ consumes more energy per gram of tissue than the heart. [115]

As the mitochondria are the intracellular sites of ATP (energy) production, significant research has been directed at finding ways to reverse or lessen "mitochondrial dysfunction." [116] Most cases of mitochondrial dysfunction are due to the increased oxidative stress resulting from chronic infection and toxin accumulation, although rare genetic defects in mitochondrial function can result in the same clinical pictures of decreased energy production. [117]

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:

• Brain disorders, including Parkinson's disease and Alzheimer's disease, stroke, and depression [149-152]
• Autism [153]
• ADHD (Attention Deficit Hyperactivity Disorder) [154]
• Hypertension (high blood pressure) [155-158]
• Coronary artery disease (atherosclerosis) and acute myocardial infarction [159-162]
• Improved clinical outcome post-coronary bypass and post-coronary angioplasty [163,164]
• Atrial fibrillation [165]
• Asthma [166,167]
• Obesity [168]
• Fibromyalgia [169]
• Diabetes (improved glucose and lipid profile) [170]
• Multiorgan failure when genetically deficient [171]
• Improvement in chronic kidney disease [172]
• Chronic lung disease [173]
• Fatty liver disease [174]
• Chronically increased oxidative stress [175]
• Vertigo [176]
• Sepsis and any critical illness [177-179]
• Statin cardiomyopathy [180]
• Statin myopathy (skeletal) [181]
• Eye disease [182]

As CoQ10 is one of few vital antioxidants that is synthesized in the body, aging accounts for much of its deficiency in the body. Older people make less CoQ10, generally have less of it in their diet, and have other medical conditions excessively consuming it. The average 80-year-old has only about 50% of the cardiac CoQ10 content as the average 20-year-old. [183,184] But its importance in cardiac function is the same regardless of age. Just as deficient hormone levels need to be restored to optimize health in the aging patient, CoQ10 needs to be similarly addressed as well, as it is essential for the optimal health of all cells. [185]

Additional supplementation can specifically target complexes I, II, and IV in the mitochondrial ETC to help optimize ATP production. Not only will such supplementation be of benefit in all the cells of the body, the increased ATP demands of the heart make them especially suited to help support and improve the failing heart. [186]

NAD (nicotinamide adenine dinucleotide) is the primary substrate fueling complex I. The primary way to keep NAD levels high, in addition to directly supplementing NAD itself, is to take large amounts of its primary precursor for being synthesized in the body. This role is served by niacin (vitamin B3) and its vitamers (like niacinamide). [199] Levels of both NAD and ATP have been documented to be significantly depressed in cardiomyopathy biopsy specimens. [187] Like CoQ10, niacin significantly improves all cardiovascular conditions, not just cardiomyopathy. [188-198]

A severe niacin deficiency state has also been documented to be the root pathology in schizophrenia and other brain disorders, consistent with the high ATP requirements of the central nervous system for normal function. [199] Severe niacin deficiency results in pellagra, a life-threatening condition that is also associated with diminished heart contractility. [200-202]

Riboflavin (vitamin B2) also plays a critical role in optimizing mitochondrial ATP production. It serves as a precursor, or building block, for FAD, the primary electron-transferring substrate in complex II of the ETC. [203] An animal study demonstrated that riboflavin can alleviate heart failure and improve cardiac metabolism. [204] It can also lessen the amount of damage that reduced blood flow, or ischemia, will inflict on the heart. [205] A genetic deficiency of complex II results in an advanced congestive cardiomyopathy, indicating its importance in this condition. [206] When FAD is targeted as an antigen by anti-mitochondrial antibodies, a dilated cardiomyopathy results as well. [207]

Complex IV of the ETC, involving the transfer of electrons via cytochrome c oxidase to oxygen, the terminal electron acceptor, is supported strongly by methylene blue (MB). [208] MB is a powerful redox dye that has been shown to benefit neurodegenerative diseases by increasing mitochondrial energy production. [209-212] Promoting ETC ATP production by directly supporting complex IV is especially significant since the oxidative stress generated in the first three complexes is avoided. This means that less net oxidative stress in generated in the cell without compromising ATP production, a rarely achieved therapeutic goal. [213] This effect is also why MB has been promoted as an anti-aging agent, as cumulative oxidative stress is the reason for all aspects of aging. [214] In cellular studies, MB clearly delays the process of aging. [215]

Consistent with its documented brain benefits, MB has also been shown to protect and heal the heart. Well-documented to completely rescue and cure patients with advanced treatment-refractory septic shock as a monotherapy, MB was also able to improve cardiac function in a septic shock patient who already had an advanced cardiomyopathy. [216-218] Other studies have confirmed this consistently positive effect of MB for septic shock. [219,220] Advanced states of hemodynamic shock without sepsis have also been resolved by MB treatment. [221] In animal studies, MB not only improves ETC energy production, it also decreases oxidative stress and improves NAD levels in the mitochondria. [222,223]

Cardiomyopathy Treatment

The proper treatment of any form of cardiomyopathy, but especially advanced congestive heart failure due to an enlarged and poorly contracting heart, needs to be directed primarily at:

1. Toxin elimination
2. Restoring normal cellular energy production

Toxin Elimination: A thorough diagnostic work-up is always optimal, although currently unlikely to occur as endomyocardial biopsy is rarely done, except to monitor for microscopic evidence of organ rejection following a heart transplant. And when it is performed, the measurement of heavy metal content is never a routine part of the examination. A provoked urine challenge test with an established chelation agent such as EDTA (ethylenediaminetetraacetic acid), DMSA (dimercaptosuccinic acid) or DMPS (dimercaptopropanesulfonate) often results in a significant release of multiple heavy metals, and it should be routinely be part of a cardiac failure workup. [224]

Mercury is detected in most people although it is often given little regard because no "obvious" mercury exposures are evident. However, the number of people exposed for many years to outgassing mercury amalgam dental fillings is enormous, and the astronomical levels of mercury found in many IDCM patients are nearly always secondary to these fillings. [225-228] Furthermore, a brisk release of mercury on urine chelation challenge should never be disregarded as inconsequential.

Hair analysis can also be very useful in evaluating heavy metal content in the body and should be done along with the provoked urine challenge. For example, autistic children had significantly higher levels of mercury, lead, arsenic, antimony, and cadmium compared to controls. [229] In another study, DMSA was shown to be effective in increasing mercury and antimony excretion in children with autism spectrum disorders. [230]

Heavy metal chelation is still rarely done, although it should logically become part of the standard-of-care treatment protocols for most medical conditions and diseases, even in the absence testing for heavy metal accumulation.

Antimony bears some additional attention, as its levels inside IDCM hearts were stunningly elevated as well. [48] Generally given little attention, antimony is as toxic, or even more toxic, than arsenic. [231] Finding IDCM heart muscle with 22,000 times the normal level of mercury and 12,000 times the normal levels of antimony must not be disregarded as a curiosity, but must be regarded as the major reason for the decreased heart function, and treated with that in mind. Significant antimony exposure is difficult to avoid, as levels in the air and water continue to increase due to multiple sources, including the significant leaching of antimony from plastic containers. [232-235]

Until definitively established otherwise, an enlarged and poorly-contracting heart (advanced congestive cardiomyopathy) must be assumed to be secondary to mercury and antimony accumulation in the heart muscle.

As discussed at length above, the evidence indicates that cardiomyopathies can been assumed to have significant heavy metal accumulation and/or ongoing low-grade chronic inflammation. Also, toxin presence in the form of spike protein accumulation will be encountered with increasing frequency in this continuing COVID pandemic.

Regardless of any test results, all cardiomyopathy patients should be taking one or more chelating, or toxin-mobilizing, agents. Furthermore, follow-up blood, urine, and/or hair testing should be done to establish that toxins are being mobilized because of the chelator administration. When testing clearly indicates high levels of one or more heavy metals in the heart, potent prescription chelation administration is often advisable, especially when heart failure is advanced. Such agents include, but are not limited to, the following: [236]

• EDTA (orally, intravenously; calcium disodium EDTA best choice)
• DMSA (orally; especially good for mercury and antimony) [237,238]
• DMPS (intravenously-very potent, can cause substantial detox symptoms)
• Dimercaprol (British anti-Lewisite [BAL]) [239]
• Penicillamine
• Deferoxamine
• Trientine (especially copper)

Important nutrient chelators or toxin mobilizers:

• Organic acids, including alpha lipoic acid, citric acid, and ascorbic acid [240-243]
• NAC (N-acetylcysteine)
• Glycine
• IP6 (inositol hexaphosphate)
• Carnitine [244]
• As much of a wide variety of antioxidants as is feasible, including bioflavonoids, amino acids, and any supplement or food with a high organosulfur content. [245] Most chelators, including the prescription agents, are synthetic amino acid derivatives . [246]

Cellular Energy Production: All cardiomyopathies have deficient to severely deficient mitochondrial production of ATP. While a broad spectrum of quality supplements is always beneficial for any disease or medical condition, specific supplementation with a sufficient dosage is required to optimize ATP production in the cells of the heart. A suggested regimen of supplementation to achieve this goal would be as follows:

• Vitamin C as ascorbic acid or sodium ascorbate, three to nine grams daily
• Magnesium, any of multiple forms, one to three grams daily
• Vitamin D3, 3,000 to 10,000 units daily, with a blood level target of 50 to 100 ng/cc

These three supplements are essential baseline supplements, as each one works to lower intracellular calcium levels, decrease oxidative stress in all cells, and to decrease all-cause mortality. [247-252]

Supplements to stimulate and support mitochondrial ATP production:

• Niacinamide, one to three grams daily (or NAD supplementation)
• Riboflavin, 200 to 400 mg daily
• Coenzyme Q10 (ubiquinone or ubiquinol), 300 to 900 mg daily
• Methylene blue, 10 to 25 mg daily

The seven supplements above should be taken by all cardiomyopathy patients. As ATP is important in all cells of the body, these seven supplements can also produce significant clinical benefits in nearly all other medical conditions as well. The following nutrient supplements also support mitochondrial ATP production and can be added to the overall chelation/supplementation protocol as desired:

• Tyrosine (a CoQ10 precursor)
• Selenium (often depleted in cardiomyopathy)
• Succinate [253]
• 5-aminolevulinic acid (supports cytochrome c oxidase function) [254]
• Glycine (helps produce 5-aminolevulinic acid) [255]
• Ribose (rate-limiting precursor for adenine nucleotide synthesis and ATP production) [256]
• Carnitine (increases ATP; its deficiency also induces cardiomyopathy) [257,258]

All dosing of prescription and supplemental agents should be under the guidance of the healthcare practitioner managing the care of the patient. The above agents are intended to be a general guide only. Clinical response and serial changes in laboratory testing are the main ways to determine how well a given patient is responding.

Recap

The heart muscle in all cardiomyopathies is depleted in ATP, the most important energy-producing molecule in the body. The worse the cardiomyopathy, the more severe the depletion. Nearly all the time, this ATP-depleted state is precipitated and maintained by heavy metal accumulations, often accelerated by earlier pathogen-provoked myocardial inflammation (myocarditis). Such myocarditis is typically undetectable on routine chemistries, and only more invasive testing can clearly document it.

When a patient presents with an enlarged, poorly contracting heart, it must be assumed that significant heavy metal accumulations are present and the treatment protocol must include chelation/toxin mobilization therapy.

Depending on the patient history and laboratory findings, the clinician needs to decide whether chronic COVID with low-grade spike protein-mediated inflammation is a major (or entire) part of the pathology involved. If this is confirmed, or if clinical suspicions are high, measures to eradicate the spike protein should be vigorously pursued. [80-83]

In addition to the heavy metal/toxin removal measures, targeted supplementation designed to directly support and heal the failing ability of the cardiac mitochondria to produce normal levels of ATP is essential for an optimal cardiac and clinical response.

Even if there is refusal to acknowledge the likely presence of heavy metals in the failing heart muscle, which will continue to be the rule rather than the exception among traditional cardiologists, non-prescription nutrient chelators and ATP production promoters can still be taken as desired, and substantial benefit will result most of the time.

Thomas E. Levy, MD, JD is a former Assistant Professor of Medicine at Tulane Medical School and a past Fellow of the American College of Cardiology. He is also a bar-certified attorney. He can be reached at televymd@yahoo.com. All his articles for the Orthomolecular Medicine News Service can be accessed at https://www.tomlevymd.com/health_ebytes.php.

Note: To access any of the references below, type in the PMID number following the citation in the search box at this link: https://pubmed.ncbi.nlm.nih.gov/.

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Albert G. B. Amoa, MB.Ch.B, Ph.D. (Ghana)
Seth Ayettey, M.B., Ch.B., Ph.D. (Ghana)
Ilyès Baghli, M.D. (Algeria)
Barry Breger, M.D. (Canada)
Ian Brighthope, MBBS, FACNEM (Australia)
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Ron Ehrlich, B.D.S. (Australia)
Hugo Galindo, M.D. (Colombia)
Gary S. Goldman, Ph.D. (USA)
William B. Grant, Ph.D. (USA)
Claus Hancke, MD, FACAM (Denmark)
Patrick Holford, BSc (United Kingdom)
Ron Hunninghake, M.D. (USA)
Bo H. Jonsson, M.D., Ph.D. (Sweden)
Dwight Kalita, Ph.D. (USA)
Felix I. D. Konotey-Ahulu, M.D., FRCP (Ghana)
Peter H. Lauda, M.D. (Austria)
Fabrice Leu, N.D., (Switzerland)
Alan Lien, Ph.D. (Taiwan)
Homer Lim, M.D. (Philippines)
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Pedro Gonzalez Lombana, M.D., Ph.D. (Colombia)
Victor A. Marcial-Vega, M.D. (Puerto Rico)
Juan Manuel Martinez, M.D. (Colombia)
Mignonne Mary, M.D. (USA)
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Karin Munsterhjelm-Ahumada, M.D. (Finland)
Sarah Myhill, MB, BS (United Kingdom)
Tahar Naili, M.D. (Algeria)
Zhiyong Peng, M.D. (China)
Isabella Akyinbah Quakyi, Ph.D. (Ghana)
Selvam Rengasamy, MBBS, FRCOG (Malaysia)
Jeffrey A. Ruterbusch, D.O. (USA)
Gert E. Schuitemaker, Ph.D. (Netherlands)
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Han Ping Shi, M.D., Ph.D. (China)
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Andrew W. Saul, Ph.D. (USA), Editor-In-Chief
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