Welcome to the Afibber’s Forum
Serving Afibbers worldwide since 1999
Moderated by Shannon and Carey
 |
 |
 |
 |
 |
 |
Home
>
AFIBBERS FORUM
>
Topic
Mitochondrial Function - Oxidative damage, Aging, Arrhythmia and more
Posted by Jackie
|
Mitochondrial Function - Oxidative damage, Aging, Arrhythmia and more December 11, 2018 12:42PM |
Registered: 6 years ago Posts: 18,881 |
Mitochondrial Function - Oxidative damage, Aging, Arrhythmia and more
Why we need to know how to keep our mitochondria healthy and functional.
This is an informational “Awareness Alert” report on a very important topic, in a non-traditional format.
I’ve been gathering information on mitochondrial function (and damage) for many years and am offering this overview to stimulate reader interest to learn more through your own independent study by using this report as a guide to relevant research links. If I detailed even just the core, important points, I’d be writing a large book, so this format offers highlights on major points including function, damage and nutritional support so those interested can follow the references for more specific details.
While the topic of mitochondrial dysfunction is by no means a new discovery, it has become a common thread in many current health news reports and advisories about healthy aging because heightened interest and more recent findings are continuing to make the case for supporting mitochondrial health as a ‘core issue.’ It’s both important and encouraging because we don’t commonly receive this type of advice during our medical wellness visits… that is, the value of optimizing healthy mitochondrial function. The referenced 2013 viewpoint by Dr. Vasquez on Mitochondrial Dysfunction and the Emerging “Mitochondrial Medicine” in section VI. is definitely worth noting.
We want to exercise and also support our “mito” health so whether you are a current Afibber, former Afibber or never an Afibber, this is important information; and especially so, for endurance athletes and ‘weekend warriors.’
Healthy regards to all,
Jackie
I. Introduction - Mitochondria
II. Root Cause Medicine – Symptoms vs. Etiology
III. How Many Mitochondria?
IV. Nutritional Support – Coenzyme Q10 and more
V. Lipid Replacement Therapy
VI. Closing and Future Reflections
VII References and Resource Reading
I. Introduction
What are Mitochondria?
First, a Cell Biology 101 snapshot describing mitochondria, how they function, why they are of critical importance for overall health, how they easily become damaged and contribute to a variety of dysfunctions in the body. Lately, more links to many neurological ailments related to mito dysfunction are in the literature; and when reading about those, there’s a logical connection
to cardiac mitochondria as well.
Mitochondria (called ‘organelles’) are structures located inside most cells which function as microscopic energy-producing components often called ‘power plants of the cells,’ and are more highly-concentrated in cells of the heart, brain, muscle tissue, liver, kidney and inner segment of rods and cones in the retina.
Healthy mito function is fundamental to health and longevity and is especially relevant to those who have experienced arrhythmia because of the heart’s a high density of these organelles. You’ll notice that in descriptions of mito dysfunction, various cardiovascular ailments are mentioned and I’ve included a few (of many) studies connecting mito damage to arrhythmia.
The ‘big reveal’ is… that by understanding the physiology of mito function and the oxidative-stress damage factor, it’s logical (and easy) to make the connection to atrial fibrillation. So be sure you scan the study references that connect those dots.
The ‘aging’ term requires clarification.
Typically, we think of aging as related to the elderly but physiologists tell us that certain cells and the production of various enzymes can have a finite supply. Example: one systemic enzyme is known to have production limits starting around age 27… hardly considered “elderly”… and other high-energy-demand cells and organelles such as mitochondria have limits based on common, intrinsic damage factors or lack of core nutrients that support optimal function and limit damage. One report noted mito are “thought to decline at around 10% per decade from our thirties and beyond.” So, this information will be noteworthy for the majority of our forum readers. Again…whether you are a current or former Afibber… or never an Afibber.
A recent report observes:
Over the last decade, scientists have begun to recognize the link between mitochondrial function (or decline of function) and our health and certain diseases. It is becoming increasingly apparent that our overall health and even how fast we age are closely related to how well our mitochondria are functioning. (1)
Mitochondria are double-walled and have their own DNA (mtDNA). As energy producers for cellular respiration, they are responsible for the process that generates the energy molecule, ATP (adenosine tri-phosphate) in the Kreb’s cycle(2) and in the electron transport chain by extracting energy from sugars and fats with the help of oxygen. Note that current thinking on fuels for ATP energy production now focuses principally on metabolizing fats rather than carbs and relates to the rise in support for adapting to the Ketogenic lifestyle and its many health benefits. (Confirming what GeorgeN has been sharing with us about his success in become Afib free by way of Ketosis.)
The mitochondria’s own (intrinsic) production of oxidative stress, ROS aka Reactive Oxygen Species, occurs during the ATP production process and is said to be around 90%.... which leaves only 10% to do a lot of heroics in the body 24/7 ….over a lifetime….plus overcoming the additional oxidative stress damage that results from endurance exercise, over-exercise, poor food choices and other lifestyle choices as well as the aging process, itself. (3). To reduce the mitochondrial oxidative stress damage, appropriate antioxidants are needed in an abundance.
Free radical damage or oxidative stress damage can be thought of as “rust”….… everyone knows what oxidation looks like…whether it is rusty metal from exposure to the elements or raw vegetables or fruit left on the counter, exposed to air, that turn brown or oxidize. The same process goes on in our body and unless we take measures to help limit and/or (better) prevent the oxidative damage, cells can die, rust, be rendered mostly nonfunctional; and if it’s mitochondrial DNA, then functional outcomes of that are impaired or rendered nonfunctional or mutated. There is support for the ROS connection and Arrhythmia. Especially telling is the connection to “ROS and aberrant Calcium handling.” (3)
In the classic report, published in Scientific American (1997), Mitochondrial DNA in Aging and Disease, PhD researcher, Douglas W. Wallace, details the function of mitochondrial DNA. The mtDNA codes for enzymes required for ATP synthesis. Errors in this DNA tend to accumulate with age, reducing ATP synthesis and increasing diseases of energy-dependent tissues and organs.(4)
Dr. Wallace: “Most human genes reside inside the nucleus of the cell, but some are also found in the energy-generating structures called mitochondria. These genes have already been linked to dozens of diseases and could prove particularly important in age-related disorders, such as Alzheimer's disease.”
At the end of this report, the Reference section provides links to the quoted and referenced material as well as additional links on the specific topics discussed in each segment so you can track the details and fill in the ‘picture’ for your own unique status.
I’d suggest you begin by reading the first few references links which are reports about mitochondrial function so you have a general overview so the other added details will make sense and help ‘connect the dots’ to make the case for the importance of keeping our ‘mito’ healthy and functional.
Before starting the layers of supporting data, this next segment points out an important treatment consideration that emphasizes the “functional focus” which is the philosophy of Functional (metabolic) Medicine practitioners for fundamental health management which emphasizes the practice of “root cause medicine” rather than just treating symptoms with meds and surgery.
II. Root Cause Medicine
Symptoms vs. Etiology:
In a post in early May on the topic, RF Balloon Ablation’ now being trialed, a comment by Pompon observed that.. “ablation didn’t address the underlying cause of AF” which was countered by Carey who said, “Afib isn't a disease -- it's a symptom of a disease and that disease is atrial myopathy.”
My comment: Well, that doesn’t take it quite far enough. We should be looking at causes of cardiac mitochondrial myopathy.
So let’s briefly explore “myopathy” in terms of mitochondrial damage underlying atrial fibrillation and the many other functionality ailments as well.
A typical definition of any type of myopathy… myo meaning muscle and pathy (aka pathos) meaning ‘suffering or disease’ would indicate that atrial myopathy is yet another symptom of an ‘ailment’ for which the underlying cause needs to be determined. (5)
All too often, symptoms of health ailments are treated without tracking down the actual cause or etiology of the symptoms which often means that while those symptoms may be managed or put in the background (with meds/surgery), the underlying cause or initiator of the complaint or condition remains ‘at large’ in the body and available to cause another malfunction and/or symptoms in another part of the body, organ or tissue.
So with atrial fibrillation, there are a variety of potential, contributing causes but nothing definitive about remedies for correcting at the “core-cause” level beyond medications and ablation procedures as standard medical treatments. Therefore, this post calls attention to investigating the deeper, underlying causes of myopathy (as just one example), that might underlie atrial fibrillation.
As motivational support for this investigative approach, take a moment to note the following observation by Mark Hyman, MD who is the Director for the Cleveland Clinic Center for Functional Medicine, Chairman of the Institute for Functional Medicine and Founder of The UltraWellness Center, Lennon, Mass. which supports looking deeper at the underlying causes of symptoms rather than just treating symptoms that may not address core defects.
Quote: My medical school training gave me the ability to diagnose thousands of different separate diseases. Diseases, I suggest, which don’t really exist in the way we think they do. We give names to disease like depression or ADD, but that just helps us group people together who have the same symptoms for the purposes of giving them all the same drug therapy. But what if I were to tell you, that new scientific discoveries tell us that there is no such thing as depression?
What we see as the symptoms of depression are reflections of a few common interconnected imbalances in the body that have nothing to do with the medical specialties, as we know them. Depression is not a psychiatric illness, but a systemic disease. To address it, we need to address the whole system—the ecosystem of your body.
That means we need to understand how the WHOLE body operates as a system, not just how different pieces of the body operate independently from one another. We need to treat people, not body parts; we want to treat the causes of disease, not symptoms. I was trained according to the dogma of separate medical specialties—for heart problems you see the cardiologist, for stomach problems you see the gastroenterologist, for joint pain you see the rheumatologist, for skin problems, the dermatologist. You just don’t ask the skin doctor about your joint pain. If you do ask, they will cut you off and tell you to see the joint doctor.
The roadmap I was given in medical school to navigate through the territory of illness was the WRONG map. It taught us to diagnose disease and then assign standardized treatments no matter who was suffering. This is the wrong approach. It’s a map that sends you in the wrong direction.
Not only are your joint pains, skin rash, irritable bowel, and depression all connected, but the ONLY way to to find your way out of this mess of chronic disease (which affects 162 million people) is by using a new map—one that allows us to see how everything is connected.
This is what the rich, new method called Functional Medicine offers. Functional Medicine applies the science of systems biology in a practical setting. It is the revolutionary new system I have been talking about. It’s a fundamental change in our thinking, a whole different paradigm, like the world-is-round-not-flat shift. It changes our approach to the very way we think about illness and the human body.
With it, we can truly treat and cure disease.
Unlike conventional medicine, Functional Medicine personalizes treatment based on a patient’s unique needs. We are all different. We have a different genetic makeup. As a result our bodies react to our environment in different ways. Understanding this allows us to develop unique methods to treat people, not diseases.
At the heart of this paradigm shift are the 7 keys of UltraWellness.(6) End quote.
Dr. Hyman also has a report on the importance of magnesium in mitochondrial health. See Reference 6
Another well-known Functional Medicine practitioner, Dr. David M. Brady has over 27- years of experience as an integrative practitioner and an academic. He is a licensed naturopathic medical physician in Connecticut and Vermont and a board-certified clinical nutritionist. He is Chief Scientific/Medical Officer for Designs for Health and serves as the Vice Provost for the Division of Health Sciences and Director of Human Nutrition Institute at the University of Bridgeport in Connecticut. (7)
Dr. Brady writes:
…... “It has been well established in the scientific medical literature that mitochondrial dysfunction, with its associated ATP deficiency, is related to a host of diseases, including degenerative neurological disorders (i.e., Alzheimer’s, Parkinson’s, multiple sclerosis, amyotrophic lateral sclerosis), cardiovascular disease (i.e., heart attack, stroke, peripheral vascular disease), obesity, and diabetes (reduced mitochondrial biogenesis has been demonstrated in metabolic syndrome). Dr. Brady notes that a regimen of certain nutritional supplements are found to benefit a variety of ailments caused by diminished mitochondrial energy production including: “Mitochondrial genetic mutations, either inborn or acquired during aging or due to excessive exercise (such as mitochondrial myopathy).”
“Mitochondria deteriorate with age due to ongoing exposure to free radicals which accelerate the destruction of cellular components. As the mitochondrial function declines, the cells become starved for energy and damaged, causing them to function less efficiently. Many investigators suspect that caloric restriction slows aging primarily by lowering free-radical production in mitochondria. Conversely, the benefits of increased mitochondrial biogenesis and ATP availability are many, including the reduction of oxidative stress and age–related deterioration as well as improvements in metabolic function, energy level, exercise performance, body composition, cognitive function, and lifespan (shown in animal models).” (7) (The specific nutrients are covered in a separate segment.)
III. How Many Mitochondria?
How many cells in the body and how many mitochondria? While this isn’t critical to this report, it’s worth mentioning because few are aware of the extremely high count of cells or mitochondria in those cells. There are various opinions on both counts…. but the generalities are typically similar to this observation:
Integrative Cardiologist, Stephen T. Sinatra MD, F.A.C.C., F.A.C.N., C.N.S., C.B.T., who is a board-certified cardiologist, certified bioenergetic psychotherapist, and certified nutrition and anti-aging specialist describes the function mitochondria this way:
“Just as a car runs on gasoline, your cells run on ATP (made in the mitochondria). So…
What cells have the most mitochondria? It’s your heart muscle cells – with about 5,000 mitochondria per cell – that contain far more mitochondria than any other organ in body! That’s because the constantly-beating heart works harder than any other organ in your body! Heart muscle cells have extra-special demand for ATP to keep the heart pumping 24/7 over a lifetime. By comparison, the tissue of the biceps muscle has about 200 mitochondria per cell.” (8)
Elaborating on that number a bit more -- a mind-boggling factoid:
The estimates are that the body has 100,000 trillion mitochondria… that need to be protected from intrinsic damage and also need nutrients to support the high-energy production process.
Approximately 10 million billion total: ~10% of body weight.
If you search online for the number of mitochondria or number of cells in the body, you’ll come up with a variety of statements by scientists on calculated estimates that serve to highlight the importance of keeping cellular structures well nourished and health and functional.
This report by Dr. Sinatra titled Metabolic Cardiology: The Missing link in Cardiovascular Disease, helps clarify importance of and the complexity of the mitochondrial function. Be sure to read the entire report. (8)
The importance of supporting energy production in heart cells
and the preservation of the mitochondria in these cells will be
the focus of a new frontier in cardiovascular prevention, treat-
ment, and management. Many physicians are not trained to
look at heart disease in terms of cellular biochemistry; there-
fore, the challenge in any metabolic cardiology discussion is in
taking the conversation from the “bench to the bedside.” An
understanding of the vital role that adenosine triphosphate
(ATP) plays in the heart is critical for any physician or clinician
considering therapeutic options that support ATP production
and turnover in jeopardized cardiac muscle cells.
Metabolic therapies that help cardiomyocytes meet their
absolute need for ATP fulfill a major clinical challenge of pre-
serving pulsatile cardiac function while maintaining cell and
tissue viability. D-ribose, L-carnitine, and coenzyme Q10 work
in synergy to help the ischemic or hypoxic heart preserve its
energy charge.
This article introduces how ATP, diastolic heart function, and
metabolic support help maintain cardiac energy by preserving
ATP substrates. Part 2 will investigate an in-depth biochemical
discussion of congestive heart failure with physiologic,
pathophysiologic, and treatment considerations.
(Altern Ther Health Med. 2009;15(2):48-50.)
Clips from this report:
The acute or chronic loss of energy substrates, mitochondrial dysfunction, and disruption of normal energy utilization and supply create conditions of reversible changes in the cell’s biochemical state. Four theories have been advanced that relate to the biochemical changes contributing to the pathology of cardiac disease: (1) a critical energy loss, (2) a critical accumulation of cellular calcium (3) the effects of free radical formation and (4) injurious effects of the accumulation of long-chain acyl compounds.
Clearly, a metabolic approach that derives enzymatic reactions in a preferential direction helps to support and restore the vulnerable heart. Such biochemical/metabolic interventions that improve energy metabolism in heart cells will offer the clinician new and exciting treatment options for patients at risk for cardiovascular disease, as well as for patients at any stage of the disease. Once an appreciation of how ATP repairs and restores heart cells is realized, targeted biochemical interventions to support ATP production and turnover will be embellished by physicians.[[/i]/size]
IV. Nutritional Support
Coenzyme Q10
“Coenzyme Q10 is probably the most widely used cofactor for treating mitochondrial-related diseases. CoQ10 functions as an electron carrier in the inner mitochondrial membrane, transferring electrons from complexes l and ll to complex lll. In addition to increasing biosynthesis of ATP (universal energy molecule), and acting as a potent free- radical scavenger, CoQ10 also reduces lactic acid levels, improves muscle strength and decreases muscle fatigability.” (9a)
There’s a variety of potentials, but fundamental to the whole process is the fact that to be fully functional, muscle tissue… be it skeletal or cardiac…needs a fuel source in the Kreb’s cycle to produce ATP or Adenosine 5’-tri-phosphate (ATP). And in order for ATP to be produced efficiently and in the quantity required to meet the body’s ATP production requirements for the Kreb’s cycle where Coenzyme Q10 or ubiquinone is utilized, the raw materials have to be available. CoQ10 is a core nutrient for the ATP production as well as the additional function as an antioxidant. CoQ10 is available from some foods but in very small amounts compared to the body’s requirements as well as how much additional is needed to for the antioxidant function to quell the oxidative damage. Aging creates more demand as does a high-energy output such as endurance exercise.
The pioneer researchers on the function of Coenzyme Q10 which is the core nutrient of mitochondria to produce the energy molecule ATP for heart failure include Prof. Frederick Crane, Drs. Karl Folkers, William Judy, Per Langsjoen, Peter Langsjoen, Gian Paolo Littarru - just a few of many and date back to 1957 when Dr. Crane isolated CoQ10 from beef hearts. There’s a brief historical chronology at footnote 9b. Years later in 1995, Italian researcher and Medical Doctor, Gian Paolo Littarru, wrote Energy and Defense, a slim, illustrated masterpiece of “Facts and perspectives on CoEnzyme Q10 in biology and medicine.” It’s a wealth of information in just 85 pages and 129 study references. Dr. Littaru is a prolific researcher participating in 141 studies listed Pub Med alone. Be sure to check the additional links
Reference 9c.
Note: For current CoQ10 supplement discussions, be aware of the ongoing marketing controversy over the form. In Reference 9 b, I’ve included the web link to a report by William V. Judy, PhD, leading CoQ researcher titled, “Coenzyme Q10 Facts or Fabrications” that helps clarify the claims for the ubiquinone form versus the ubiquinol form. At least 10 years ago, Alan R. Gaby, MD, said in a webinar on CoQ10 that the original version… the Ubiquinone (oxidized form) worked well and he didn’t see justification for spending 10 times that much for the reduced form, Ubiquinol. So, I’ve provided the Facts/Fabrications piece for support as well. There are numerous reports and various studies that say the ‘nol’ form is found to be more effective. So, FYI and be aware. The main point is to take enough. Some doctors say, “take as much as you can afford.”
Statins Deplete CoQ10 - Even though CoQ10 is available in some foods, the majority of CoQ10 is biosynthesized from other nutrients in the body. Although CoQ10 is naturally produced, a person may become unable to make the needed amount of CoQ10 due to aging, neurological disorders, cardiovascular disease, diabetes mellitus, certain cancers, gum disease, and the use of a “statin” or anthracycline medication. Since CoQ10’s discovery in 1957, it has become evident that many people develop deficiencies of this naturally-occurring nutrient. Deficiencies of CoQ10 are found in older individuals, people with neurological disorders or cardiovascular disease, and in people who are taking a “statin” cholesterol lowering drug or anthracycline medication. Source: 2008 ProThera product info bulletin
Additional mitochondrial support nutrients
Following is a list of additional nutrients known to enhance bioenergetic pathways within the mitochondria, prevent intra-mitochondrial free radical activity and maintain cell membrane integrity and fluidity…including the Krebs cycle and the electron transport chain. One notation indicated the combination of various supportive nutrients may benefit mitochondrial genetic mutations, either in-borne or acquired during aging or due to excessive exercise (such as mitochondrial myopathy) (9d)
One relatively new and popular substance is pyrroloquinoline quinone (PQQ), a water-soluble, vitamin-like compound designed to help support optimal mitochondrial biogenesis, which is critical for the promotion of healthy aging, optimal energy production, and protection from reactive oxygen species (oxidative stress). PQQ is a water-soluble, vitamin-like compound and an enzyme cofactor possessing antioxidative, neuroprotective, and cardioprotective properties that encourage mitochondrial biogenesis. [The product I use from Designs for Health (MitoPQQ) includes Rhodiola rosea that helps support the adrenal glands.] Research shows that Rhodiola rosea is a powerful herb for enhancing mitochondrial energy production and helps defend against free radicals in the nervous system as well as the mitochondria. Life Extension magazine offers reports on the PQQ in their product line.
There are several combination products which I like to call a ‘multi’ for mito health… One is Mitochondrial NRG ™ by Designs for Health and another is MitoThera(TM) by Klaire Labs, Life Extension offers Mitochondrial Basics with PQQ, and Researched Nutritionals offers ATP Fuel for mitochondrial/Kreb’s cycle support that includes NT Factors for cell membrane support.
Additional Mito Support Nutrients:
Acetyl L-Carnitine: Supports energy production and membrane function
Quercetin: Protects mitochondria against lipid peroxidation
Magnesium: Crucial to ATP production
Creatine: Helps maintain ATP levels
Alpha-lipoic Acid: Supports mitochondrial enzymes and extends antioxidant protection
Red Grape Extract: Potent antioxidant activity
N-Acetyl-L-cysteine: Counteracts cellular stress
Lecithin/Phosphatidylcholine: Maintains membrane fluidity
Malic Acid and Succinic Acid: for refilling of key Krebs cycle intermediates
Taurine to protect against differing types of free radicals both inside and outside of cells
Pantethine – needed to shuttle fats from blood stream across cellular membrane for entry
L-Carnitine – necessary to shuttle those same fats across the mitochondrial membranes for brning
B-vitamins, magnesium and manganese – required as Krebs cycle enzyme cofactors
Ribose – a nucleotide repleter and direct cellular energy source
Resveratrol and Curcumin – botanicals shown to induce the production of additional mitochondria (biogenesis) through SIRT1 gene signaling and PGC-1-alpha induction
V. Lipid Replacement Therapy
And, lastly: No report on mitochondrial support would be complete without addressing the very important research findings by Garth Nicholson, PhD, and Rita Ellithorpe, MD, on Lipid Replacement Therapy.
Lipid Replacement and Antioxidant Nutritional Therapy for Restoring Mitochondrial Function and Reducing Fatigue in Chronic Fatigue Syndrome and other Fatiguing Illnesses*
Garth L. Nicolson, Ph.D. and Rita Ellithorpe, M.D.
The Institute for Molecular Medicine, Huntington Beach, California, USA
Journal of Chronic Fatigue Syndrome 2006; 13(1): 57-68.
[www.immed.org]
How to Repair Mitochondria with Lipid Replacement
[thequantifiedbody.net]
Mitochondrial Dysfunction and Chronic Disease: Treatment With Natural Supplements
Garth L. Nicolson, PhD Integr Med (Encinitas). 2014 Aug; 13(4): 35–43. PMCID: PMC4566449 PMID: 26770107 [www.ncbi.nlm.nih.gov]
Membranes in Motion – The Fluid Mosaic Membrane Model (about mitochondrial membrane)
[www.clinicaleducation.org]
August 2012 - “ When mitochondrial cardiolipin and, to a lesser degree, other phosphatidyl phospholipids are damaged by oxidants, the chemical/electrical potential across the inner mitochondrial membrane is altered due to an increasingly “leaky” membrane that allows protons and ions to move across the membrane. This occurs because the oxidized membrane phospholipids no longer form a tight ionic/electrical ‘seal’ or barrier. The loss of this ionic/electrical barrier has significant effects on a number of cellular properties, such as loss of transport and cellular energy, altered metabolism and even initiation of cell death.”
The introduction to this report begins by noting: It isn’t every newsletter issue that FOCUS has the privilege of featuring a scientist whose theory of a fundamental biological phenomenon is accepted throughout the biological and medical sciences as the standard textbook model. Such is the case with S. J. Singer’s and Garth Nicholson’s landmark theory of the Fluid Mosaic Model of cell membranes. This model, proposed in 1972 and published in the prestigious journal SCIENCE, has been called a “unified theory” of the cell membrane. This model has been tested and retested for many decades, and is now believed to accurately predict the structure and behavior of all cellular membranes. Over the intervening years, this theory has been confirmed by many sophisticated physical and chemical techniques, including one known as freeze-fracture electron microscopy.
[www.clinicaleducation.org]
Why Lipid Replacement Therapy(LRT®) is Key to our Health
[www.clinicaleducation.org]
Lipid Replacement Therapy®, Fatigue and Dysbiosis – the Mitochondrial and Immune Connection
By Michael E. Ash BSc DO ND and Garth L. Nicolson, PhD 05 June 2012 [ra-infection-connection.com]
Reference 10 has an additional paper specific to mitochondria by Michael Ash, BSC, DO, ND DiplON…
Mitochondria and the Anti-Aging Role Of Lipid Replacement Therapies
Autophagy is initiated in response to cellular stresses such as nutrient starvation, oxidative stress, infection, or inflammatory stimuli. Targets of the selective autophagic machinery include organelles, protein aggregates, and even invading microorganisms. Mitochondria, which accrue damage as they age, can present a challenge to the cell through uncontrolled generation of reactive oxygen species (ROS) and become increasingly inefficient in their generation of adenosine tri-phosphate (ATP)
The selective removal of mitochondria by autophagy, known as mitophagy, is an important cellular adaptation to the challenge presented by this important organelle and the potential health hazard it represents. Equally important is the prevention of inappropriate damage and the related early repair of mitochondrial membranes to ensure that appropriate and time relevant mitophagy occurs. (10)
[[size=medium]b]VI. In Closing and Future Reflections[/b]
The intent of this post is to provide an overview and sampling of some of the many theories and practices that support the importance of healthy mitochondria for overall health including heart function as well as connecting the dots to that relating to arrhythmia. (An online search will provide more) and note that there are many very recent related studies.
This is longer than I intended. So, apologies, but it was difficult to limit length with such an abundance of compelling information available to share. Lastly:
The 2013 presentation Mitochondrial Dysfunction and the Emerging “Mitochondrial Medicine” by Alex Vasquez, D, ND, DO FACN… is an important observation worth reading as it upgrades many former philosophies and practices. The point Dr. Vasquez makes on inflammation and mitochondrial function is important… ( p. 22 of the pdf download at the link below)
Integrative Medicine • Vol. 12, No. 4 • August 2013 p 22 Vasquez—Viewpoints
Dr Vasquez:
Per my description of various inflammatory diseases in my “functional inflammology protocol,” I distinguish the three major categories of sustained/chronic inflammation as (1) metabolic, (2) allergic, and (3) auto-immune. In truth, the delineation of these categories is perceptual and conceptual rather than actual, given that significant overlap exists between states of metabolic, allergic, and autoimmune inflammation. Mitochondrial dysfunction plays a role within each of these subcategories of clinical disease.
Some of the simplest truths we can articulate to describe this landscape are (1) mitochondrial dysfunction causes inflammation, and inflammation causes mitochondrial dysfunction; (2) mitochondrial dysfunction increases free radical generation, and increased free radical generation promotes mitochondrial dysfunction via several mechanisms; and also that (3) nutrient deficiencies promote mitochondrial dysfunction, and the reverse is also true.
Lastly, in introducing the connection between inflammation and mitochondrial dysfunction, we can note that some of the so-called anti-inflammatory drugs—including the prototype prednisone—actually cause/exacerbate mitochondrial dysfunction. Thus in this situation we note the following paradox: A drug used in the treatment of inflammatory/allergic/autoimmune diseases could actually promote the same diseases via pharmaceutical-iatrogenic induction of mitochondrial dysfunction. End quote.
[www.academia.edu]
And… for a deeper dive into current philosophies regarding fundamental biophysics and mitochondrial function, check out Neurosurgeon, Jack Kruse, MD’s website at the links in Reference 11.
Once again, healthy regards (and healthy mitochondria) to all!
Jackie
VII. References and additional resource links
1. MitoQ.com
2. Kreb’s cycle… [www.cureffi.org]
Maximizing Your Body’s Performance by Ward Dean, MD and Jim English… note segment on Kreb’s cycle. [nutritionreview.org]
3. Connections to Oxidative Stress Damage and Arrhythmia + much more with an online search of those words. Here’s a start – see additional links after Ref. 10.
Understanding Oxidative Stress [www.wallerwellness.com]
Calcium and ROS: A mutual interplay Redox Biology Volume 6, December 2015, Pages 260-271
[doi.org] [www.sciencedirect.com]
Dysfunctional calcium load and oxidative stress via mitochondria and ER has been associated with myocardial infarction and other ischemic diseases. Consequently, cardiomyocytes develop hypertrophy, fibrosis, apoptosis, inflammation and structural cardiac remodeling eventually leading to cardiomyopathy and even heart failure [32]. In the aging heart, increased mitochondrial ROS result in thiol-oxidation of RyR channel hyperactivity and shortened refractoriness of Ca2+ release in cardiomyocytes. This mechanism probably plays an important role in the increased incidence of arrhythmias and sudden death in the ageing population [37].
Mitochondria and Arrhythmias
Free Radic Biol Med. Author manuscript; available in PMC 2015 Jun 1.
Kai-Chien Yang,a Marcelo G. Bonini,a,c,d and Samuel C. Dudley, Jr.* Free Radic Biol Med. 2014 Jun; 71: 351–361. Published online 2014 Apr 5. doi: [10.1016/j.freeradbiomed.2014.03.033] PMCID: PMC4096785 NIHMSID: NIHMS584382 PMID: 24713422
Abstract Mitochondria are essential to providing ATP thereby satisfying the energy demand of the incessant electrical activity and contractile action of cardiac muscle. Emerging evidence indicates that mitochondrial dysfunction can adversely impact cardiac electrical functioning by impairing the intracellular ion homeostasis and membrane excitability through reduced ATP production and excessive reactive oxidative species (ROS) generation, resulting in increased propensity to cardiac arrhythmias. In this review, the molecular mechanisms linking mitochondrial dysfunction to cardiac arrhythmias are discussed with an emphasis on the impact of increased mitochondrial ROS on the cardiac ion channels and transporters that are critical to maintaining normal electromechanical functioning of the cardiomyocytes. The potential of using mitochondria-targeted antioxidants as a novel anti-arrhythmia therapy is highlighted.
Mitochondrial oxidative stress promotes atrial fibrillation Wenjun Xie,1,* Gaetano Santulli,1,* Steven R. Reiken,1 Qi Yuan,1 Brent W. Osborne,1 Bi-Xing Chen,1 and Andrew R. Marksa,1,2
Sci Rep. 2015; 5: 11427. Published online 2015 Jul 14. doi: [10.1038/srep11427] PMCID: PMC4501003 PMID: 26169582
Redox modification of ryanodine receptors by mitochondria-derived reactive oxygen species contributes to aberrant Ca2+ handling in ageing rabbit hearts Physiol. 2013 Dec 1; 591(Pt 23): 5895–5911. Published online 2013 Sep 16. doi: [10.1113/jphysiol.2013.260521] [www.ncbi.nlm.nih.gov]
How mitochondria produce reactive oxygen species
Michael P. Murphy1 Biochem J. 2009 Jan 1; 417(Pt 1): 1–13.
Published online 2008 Dec 12. doi: [10.1042/BJ20081386]
PMCID: PMC2605959PMID: 19061483
[www.ncbi.nlm.nih.gov]
Oxidative stress: A possible pathogenesis of atrial fibrillation Medical Hypotheses Volume 72, Issue 4, April 2009, Pages 466-467 Cong-xinHuanga YuLiuaWen-fangXiabYan-hongTangaHeHuanga [doi.org] [www.sciencedirect.com]
Cellular and Molecular Mechanisms of Arrhythmia by Oxidative Stress Ali A. Sovari * Cardiol Res Pract. 2016; 2016: 9656078. Published online 2016 Feb 15. doi: [10.1155/2016/9656078 PMCID: PMC4770129 PMID: 26981310
4. The Wallace references… several… (First download the 1997 paper for a classic, foundational overview).
DOUGLAS C. WALLACE is Robert W. Woodruff Professor of Molecular Genetics and director of the Center for Molecular Medicine at the Emory University School of Medicine. He received his Ph.D. in microbiology and
human genetics from Yale University , where he and his collaborators first demonstrated that mitochondrial DNA
in human cells could encode heritable traits. Wallace has received many awards for his research on the human mitochondrial genome, including the 1994 American Society of Human Genetics’s William Allan Award for Outstanding Contributions to Human Genetics.
Mitochondrial DNA in Aging and Disease by Douglas C. Wallace (this is the classic 1997 paper)
….Defects in DNA outside the chromosomes— in cell structures called mitochondria can cause an array of disorders, perhaps including many that debilitate the elderly
Scientific American August 1007 pdf file.
[www.physics.ohio-state.edu]
Blog www.mitoaction.org/blog/wallace-mitochondrial-genetics-and-disease
Douglas Wallace, PhD won the 2017 Dr. Paul Jansen prestigious Award for Biomedical Research for his pioneering work in the field of mitochondrial genetics.
[mitochondrialdiseasenews.com]
Mitochondrial DNA in aging and disease (book) by Douglas C. Wallace (1997) [www.worldcat.org]
A mitochondrial bioenergetic etiology of disease Douglas C. Wallace J Clin Invest. 2013 Apr 1; 123(4): 1405–1412. Published online 2013 Apr 1. doi: [10.1172/JCI61398] PMCID: PMC3614529 PMID: 23543062
5. Myopathy
As an introduction, (Step 1) - check the following link for definitions of myopathy. Scan through them so you know the basics describing the condition. Here’s one of many myopathy definitions.
Source: www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/.../myopathy/
…. “Myopathy refers to a clinical disorder of the skeletal muscles. Abnormalities of muscle cell structure and metabolism lead to various patterns of weakness and dysfunction. In some cases, the pathology extends to involve cardiac muscle fibers, resulting in a hypertrophic or dilated cardiomyopathy.” [www.clevelandclinicmeded.com]
6. Mark Hyman, MD 7 keys to Ultrawellness [drhyman.com]
What the Heck are Mitochondria? Mark Hyman, MD
[drhyman.com]
Over Half the U.S. Population is Deficient in This Critical Mineral: Maximizing Your Mitochondria with Magnesium Part 1 Mark Hyman MD - [blog.wellnessfx.com]
UltraWellness Lesson 6: Energy, Mitochondria, and Oxidative Stress - Mark Hyman, MD [drhyman.com]
Dr. Hyman tells his personal story about toxins damaging his mitochondria.
[experiencelife.com]
7. David M. Brady, ND, DC, CCN,DACBN [drdavidbrady.com]
8. What are Mitochondria? Source: Integrative Cardiologist, Stephen Sinatra [heartmdinstitute.com]
Metabolic Cardiology: The Missing link in Cardiovascular Disease,
Stephen T. Sinatra, MD, FACC, FACN
[2cjz4t37rndy1lvklpf0rv9t-wpengine.netdna-ssl.com] (Part 1)
The Coenzyme Q10 Phenomenon by Stephen T. Sinatra MD, FACC, FACN
[www.goodreads.com]
Hardcover 1998
Coenzyme Q10 Benefits, Stephen Sinatra, MD
[heartmdinstitute.com]
9. Nutritional Support – Coenzyme Q10
9-a. Restoring Mitochondrial Function and Bio-energetics, Vitamin Research Products 2005, by Ward Dean MD – Reprinted @ [www.worldwidehealthcenter.net] Oct. 2016 Reference 1 – Cohen B. Gold D. Mitochondrial cytopathy in adults: What we know so far. Cleveland Clinic J. Medicine 2001 68:7, 625
Start here and scroll down to Series Four on Mitochondrial Function by Ward Dean MD for the historical background/history and views on mito function… from early 2000’s. [warddeanmd.com]
[warddeanmd.com]
Mitochondrial energy metabolism and ageing Volume 1797, Issues 6–7, June–July 2010, Pages 961-967 [www.sciencedirect.com]
9.b Coenzyme Q10 Facts or Fabrications, 2007, William V. Judy, PhD. [vitexnutrition.com]
Summary version by another website: [icqaproject.org]
This well-referenced 2010 Life Extension report “Reverse Mitochondrial Damage” offers rebuttal info on the CoQ10 forms as well as other supportive nutrient information. [www.lifeextension.com]
First drug to significantly improve heart failure mortality in over a decade
European Society of Cardiology (ESC) May 25, 2013
Summary: Coenzyme Q10 decreases all cause mortality by half, according to new results. It is the first drug to improve heart failure mortality in over a decade and should be added to standard treatment, according to experts. [www.sciencedaily.com]
9.c Good source for reference reading: [www.sciencedirect.com]
PubMed- Littarru studies [www.ncbi.nlm.nih.gov]
9. d Mito-Thera™ - Comprehensive Nutritional Support for Mitochondrial Energy Production – Spring 2010 and Mitochondrial NRG ™ supplement by Designs for Health product data sheet.
10. Mitochondria and the Anti-Aging Role Of Lipid Replacement Therapies
by Michael Ash BSc. DO. ND DipION0.
[www.clinicaleducation.org]
Mitochondrial Dysfunction and Susceptibility to Atrial Fibrillation in the Elderly
[physicianupdate.wordpress.com]
The path from mitochondrial ROS to aging runs through the mitochondrial permeability transition pore [www.researchgate.net]
Oxidative damage to mitochondrial DNA in atrial muscle of patients with atrial fibrillation Free Radical Biology and Medicine Volume 35, Issue 10, 15 November 2003, Pages 1310-1318 [doi.org] Po-HanLin*†Shih-HuangLee‡§Chia-PingSu*Yau-HueiWei*§
Exercise-induced protection against reperfusion arrhythmia involves stabilization of mitochondrial energetics. Am J Physiol Heart Circ Physiol. 2016 May 15;310(10):H1360-70. doi: 10.1152/ajpheart.00858.2015. Epub 2016 Mar 4. Alleman RJ1, Tsang AM1, Ryan TE1, Patteson DJ1, McClung JM1, Spangenburg EE1, Shaikh SR2, Neufer PD1, Brown DA3.
Oxidative Stress and Atrial Fibrillation - Finding a Missing Piece to the Puzzle One possible explanation for the limitations of current therapies is that they do not address effectively or completely the underlying causes of AF. Evidence has been mounting that AF is associated with systemic and cardiac oxidation.4,5 Kai-Chien Yang and Samuel C. DudleyJr Originally published12 Sep 2013Circulation. 2013;128:1724–1726
Cellular and Molecular Mechanisms of Arrhythmia by Oxidative Stress Ali A. Sovari Review Article Cardiology Research and Practice Volume 2016, Article ID 9656078, 7 pages [dx.doi.org]
Abstract Current therapies for arrhythmia using ion channel blockade, catheter ablation, or an implantable cardioverter defibrillator have limitations, and it is important to search for new antiarrhythmic therapeutic targets. Both atrial fibrillation and heart failure, a condition with increased arrhythmic risk, are associated with excess amount of reactive oxygen species (ROS). There are several possible ways for ROS to induce arrhythmia. ROS can cause focal activity and reentry. ROS alter multiple cardiac ionic currents. ROS promote cardiac fibrosis and impair gap junction function, resulting in reduced myocyte coupling and facilitation of reentry. In order to design effective antioxidant drugs for treatment of arrhythmia, it is essential to explore the molecular mechanisms by which ROS exert these arrhythmic effects. Activation of Ca2+/CaM-dependent kinase II, c-Src tyrosine kinase, protein kinase C, and abnormal splicing of cardiac sodium channels are among the recently discovered molecular mechanisms of ROS-induced arrhythmia.
Oxidative stress and inflammation as central mediators of atrial fibrillation in obesity and diabetes Cardiovascular Diabetology 201716:120 Basil S. Karam, Alejandro Chavez-Moreno, Wonjoon Koh, Joseph G. Akar and Fadi G. Akar [doi.org]
Mitochondrial Bioenergetics During Ischemia and Reperfusion.
Adv Exp Med Biol. 2017;982:141-167. doi: 10.1007/978-3-319-55330-6_8.
Consolini AE1, Ragone MI2,3, Bonazzola P3,4, Colareda GA5.
Oxidative stress in atrial fibrillation: An emerging role of NADPH oxidase Ji-jounYounabJunZhangabYixuanZhangabHouzaoChencDepeiLiucPeipeiPingdJames N.WeisseHuaCaiab Journal of Molecular and Cellular Cardiology Volume 62, September 2013, Pages 72-79 [doi.org]
Mitochondrial dysfunction and molecular pathways of disease
Steve R. Pieczenik, John Neustadt, ND Received 30 August 2006
[nbihealth.com]
11. Neurosurgeon, Jack Kruse, MD.
[jackkruse.com] [jackkruse.com]
[jackkruse.com]
[healthcastnow.libsyn.com]
Why we need to know how to keep our mitochondria healthy and functional.
This is an informational “Awareness Alert” report on a very important topic, in a non-traditional format.
I’ve been gathering information on mitochondrial function (and damage) for many years and am offering this overview to stimulate reader interest to learn more through your own independent study by using this report as a guide to relevant research links. If I detailed even just the core, important points, I’d be writing a large book, so this format offers highlights on major points including function, damage and nutritional support so those interested can follow the references for more specific details.
While the topic of mitochondrial dysfunction is by no means a new discovery, it has become a common thread in many current health news reports and advisories about healthy aging because heightened interest and more recent findings are continuing to make the case for supporting mitochondrial health as a ‘core issue.’ It’s both important and encouraging because we don’t commonly receive this type of advice during our medical wellness visits… that is, the value of optimizing healthy mitochondrial function. The referenced 2013 viewpoint by Dr. Vasquez on Mitochondrial Dysfunction and the Emerging “Mitochondrial Medicine” in section VI. is definitely worth noting.
We want to exercise and also support our “mito” health so whether you are a current Afibber, former Afibber or never an Afibber, this is important information; and especially so, for endurance athletes and ‘weekend warriors.’
Healthy regards to all,
Jackie
I. Introduction - Mitochondria
II. Root Cause Medicine – Symptoms vs. Etiology
III. How Many Mitochondria?
IV. Nutritional Support – Coenzyme Q10 and more
V. Lipid Replacement Therapy
VI. Closing and Future Reflections
VII References and Resource Reading
I. Introduction
What are Mitochondria?
First, a Cell Biology 101 snapshot describing mitochondria, how they function, why they are of critical importance for overall health, how they easily become damaged and contribute to a variety of dysfunctions in the body. Lately, more links to many neurological ailments related to mito dysfunction are in the literature; and when reading about those, there’s a logical connection
to cardiac mitochondria as well.
Mitochondria (called ‘organelles’) are structures located inside most cells which function as microscopic energy-producing components often called ‘power plants of the cells,’ and are more highly-concentrated in cells of the heart, brain, muscle tissue, liver, kidney and inner segment of rods and cones in the retina.
Healthy mito function is fundamental to health and longevity and is especially relevant to those who have experienced arrhythmia because of the heart’s a high density of these organelles. You’ll notice that in descriptions of mito dysfunction, various cardiovascular ailments are mentioned and I’ve included a few (of many) studies connecting mito damage to arrhythmia.
The ‘big reveal’ is… that by understanding the physiology of mito function and the oxidative-stress damage factor, it’s logical (and easy) to make the connection to atrial fibrillation. So be sure you scan the study references that connect those dots.
The ‘aging’ term requires clarification.
Typically, we think of aging as related to the elderly but physiologists tell us that certain cells and the production of various enzymes can have a finite supply. Example: one systemic enzyme is known to have production limits starting around age 27… hardly considered “elderly”… and other high-energy-demand cells and organelles such as mitochondria have limits based on common, intrinsic damage factors or lack of core nutrients that support optimal function and limit damage. One report noted mito are “thought to decline at around 10% per decade from our thirties and beyond.” So, this information will be noteworthy for the majority of our forum readers. Again…whether you are a current or former Afibber… or never an Afibber.
A recent report observes:
Over the last decade, scientists have begun to recognize the link between mitochondrial function (or decline of function) and our health and certain diseases. It is becoming increasingly apparent that our overall health and even how fast we age are closely related to how well our mitochondria are functioning. (1)
Mitochondria are double-walled and have their own DNA (mtDNA). As energy producers for cellular respiration, they are responsible for the process that generates the energy molecule, ATP (adenosine tri-phosphate) in the Kreb’s cycle(2) and in the electron transport chain by extracting energy from sugars and fats with the help of oxygen. Note that current thinking on fuels for ATP energy production now focuses principally on metabolizing fats rather than carbs and relates to the rise in support for adapting to the Ketogenic lifestyle and its many health benefits. (Confirming what GeorgeN has been sharing with us about his success in become Afib free by way of Ketosis.)
The mitochondria’s own (intrinsic) production of oxidative stress, ROS aka Reactive Oxygen Species, occurs during the ATP production process and is said to be around 90%.... which leaves only 10% to do a lot of heroics in the body 24/7 ….over a lifetime….plus overcoming the additional oxidative stress damage that results from endurance exercise, over-exercise, poor food choices and other lifestyle choices as well as the aging process, itself. (3). To reduce the mitochondrial oxidative stress damage, appropriate antioxidants are needed in an abundance.
Free radical damage or oxidative stress damage can be thought of as “rust”….… everyone knows what oxidation looks like…whether it is rusty metal from exposure to the elements or raw vegetables or fruit left on the counter, exposed to air, that turn brown or oxidize. The same process goes on in our body and unless we take measures to help limit and/or (better) prevent the oxidative damage, cells can die, rust, be rendered mostly nonfunctional; and if it’s mitochondrial DNA, then functional outcomes of that are impaired or rendered nonfunctional or mutated. There is support for the ROS connection and Arrhythmia. Especially telling is the connection to “ROS and aberrant Calcium handling.” (3)
In the classic report, published in Scientific American (1997), Mitochondrial DNA in Aging and Disease, PhD researcher, Douglas W. Wallace, details the function of mitochondrial DNA. The mtDNA codes for enzymes required for ATP synthesis. Errors in this DNA tend to accumulate with age, reducing ATP synthesis and increasing diseases of energy-dependent tissues and organs.(4)
Dr. Wallace: “Most human genes reside inside the nucleus of the cell, but some are also found in the energy-generating structures called mitochondria. These genes have already been linked to dozens of diseases and could prove particularly important in age-related disorders, such as Alzheimer's disease.”
At the end of this report, the Reference section provides links to the quoted and referenced material as well as additional links on the specific topics discussed in each segment so you can track the details and fill in the ‘picture’ for your own unique status.
I’d suggest you begin by reading the first few references links which are reports about mitochondrial function so you have a general overview so the other added details will make sense and help ‘connect the dots’ to make the case for the importance of keeping our ‘mito’ healthy and functional.
Before starting the layers of supporting data, this next segment points out an important treatment consideration that emphasizes the “functional focus” which is the philosophy of Functional (metabolic) Medicine practitioners for fundamental health management which emphasizes the practice of “root cause medicine” rather than just treating symptoms with meds and surgery.
II. Root Cause Medicine
Symptoms vs. Etiology:
In a post in early May on the topic, RF Balloon Ablation’ now being trialed, a comment by Pompon observed that.. “ablation didn’t address the underlying cause of AF” which was countered by Carey who said, “Afib isn't a disease -- it's a symptom of a disease and that disease is atrial myopathy.”
My comment: Well, that doesn’t take it quite far enough. We should be looking at causes of cardiac mitochondrial myopathy.
So let’s briefly explore “myopathy” in terms of mitochondrial damage underlying atrial fibrillation and the many other functionality ailments as well.
A typical definition of any type of myopathy… myo meaning muscle and pathy (aka pathos) meaning ‘suffering or disease’ would indicate that atrial myopathy is yet another symptom of an ‘ailment’ for which the underlying cause needs to be determined. (5)
All too often, symptoms of health ailments are treated without tracking down the actual cause or etiology of the symptoms which often means that while those symptoms may be managed or put in the background (with meds/surgery), the underlying cause or initiator of the complaint or condition remains ‘at large’ in the body and available to cause another malfunction and/or symptoms in another part of the body, organ or tissue.
So with atrial fibrillation, there are a variety of potential, contributing causes but nothing definitive about remedies for correcting at the “core-cause” level beyond medications and ablation procedures as standard medical treatments. Therefore, this post calls attention to investigating the deeper, underlying causes of myopathy (as just one example), that might underlie atrial fibrillation.
As motivational support for this investigative approach, take a moment to note the following observation by Mark Hyman, MD who is the Director for the Cleveland Clinic Center for Functional Medicine, Chairman of the Institute for Functional Medicine and Founder of The UltraWellness Center, Lennon, Mass. which supports looking deeper at the underlying causes of symptoms rather than just treating symptoms that may not address core defects.
Quote: My medical school training gave me the ability to diagnose thousands of different separate diseases. Diseases, I suggest, which don’t really exist in the way we think they do. We give names to disease like depression or ADD, but that just helps us group people together who have the same symptoms for the purposes of giving them all the same drug therapy. But what if I were to tell you, that new scientific discoveries tell us that there is no such thing as depression?
What we see as the symptoms of depression are reflections of a few common interconnected imbalances in the body that have nothing to do with the medical specialties, as we know them. Depression is not a psychiatric illness, but a systemic disease. To address it, we need to address the whole system—the ecosystem of your body.
That means we need to understand how the WHOLE body operates as a system, not just how different pieces of the body operate independently from one another. We need to treat people, not body parts; we want to treat the causes of disease, not symptoms. I was trained according to the dogma of separate medical specialties—for heart problems you see the cardiologist, for stomach problems you see the gastroenterologist, for joint pain you see the rheumatologist, for skin problems, the dermatologist. You just don’t ask the skin doctor about your joint pain. If you do ask, they will cut you off and tell you to see the joint doctor.
The roadmap I was given in medical school to navigate through the territory of illness was the WRONG map. It taught us to diagnose disease and then assign standardized treatments no matter who was suffering. This is the wrong approach. It’s a map that sends you in the wrong direction.
Not only are your joint pains, skin rash, irritable bowel, and depression all connected, but the ONLY way to to find your way out of this mess of chronic disease (which affects 162 million people) is by using a new map—one that allows us to see how everything is connected.
This is what the rich, new method called Functional Medicine offers. Functional Medicine applies the science of systems biology in a practical setting. It is the revolutionary new system I have been talking about. It’s a fundamental change in our thinking, a whole different paradigm, like the world-is-round-not-flat shift. It changes our approach to the very way we think about illness and the human body.
With it, we can truly treat and cure disease.
Unlike conventional medicine, Functional Medicine personalizes treatment based on a patient’s unique needs. We are all different. We have a different genetic makeup. As a result our bodies react to our environment in different ways. Understanding this allows us to develop unique methods to treat people, not diseases.
At the heart of this paradigm shift are the 7 keys of UltraWellness.(6) End quote.
Dr. Hyman also has a report on the importance of magnesium in mitochondrial health. See Reference 6
Another well-known Functional Medicine practitioner, Dr. David M. Brady has over 27- years of experience as an integrative practitioner and an academic. He is a licensed naturopathic medical physician in Connecticut and Vermont and a board-certified clinical nutritionist. He is Chief Scientific/Medical Officer for Designs for Health and serves as the Vice Provost for the Division of Health Sciences and Director of Human Nutrition Institute at the University of Bridgeport in Connecticut. (7)
Dr. Brady writes:
…... “It has been well established in the scientific medical literature that mitochondrial dysfunction, with its associated ATP deficiency, is related to a host of diseases, including degenerative neurological disorders (i.e., Alzheimer’s, Parkinson’s, multiple sclerosis, amyotrophic lateral sclerosis), cardiovascular disease (i.e., heart attack, stroke, peripheral vascular disease), obesity, and diabetes (reduced mitochondrial biogenesis has been demonstrated in metabolic syndrome). Dr. Brady notes that a regimen of certain nutritional supplements are found to benefit a variety of ailments caused by diminished mitochondrial energy production including: “Mitochondrial genetic mutations, either inborn or acquired during aging or due to excessive exercise (such as mitochondrial myopathy).”
“Mitochondria deteriorate with age due to ongoing exposure to free radicals which accelerate the destruction of cellular components. As the mitochondrial function declines, the cells become starved for energy and damaged, causing them to function less efficiently. Many investigators suspect that caloric restriction slows aging primarily by lowering free-radical production in mitochondria. Conversely, the benefits of increased mitochondrial biogenesis and ATP availability are many, including the reduction of oxidative stress and age–related deterioration as well as improvements in metabolic function, energy level, exercise performance, body composition, cognitive function, and lifespan (shown in animal models).” (7) (The specific nutrients are covered in a separate segment.)
III. How Many Mitochondria?
How many cells in the body and how many mitochondria? While this isn’t critical to this report, it’s worth mentioning because few are aware of the extremely high count of cells or mitochondria in those cells. There are various opinions on both counts…. but the generalities are typically similar to this observation:
Integrative Cardiologist, Stephen T. Sinatra MD, F.A.C.C., F.A.C.N., C.N.S., C.B.T., who is a board-certified cardiologist, certified bioenergetic psychotherapist, and certified nutrition and anti-aging specialist describes the function mitochondria this way:
“Just as a car runs on gasoline, your cells run on ATP (made in the mitochondria). So…
What cells have the most mitochondria? It’s your heart muscle cells – with about 5,000 mitochondria per cell – that contain far more mitochondria than any other organ in body! That’s because the constantly-beating heart works harder than any other organ in your body! Heart muscle cells have extra-special demand for ATP to keep the heart pumping 24/7 over a lifetime. By comparison, the tissue of the biceps muscle has about 200 mitochondria per cell.” (8)
Elaborating on that number a bit more -- a mind-boggling factoid:
The estimates are that the body has 100,000 trillion mitochondria… that need to be protected from intrinsic damage and also need nutrients to support the high-energy production process.
Approximately 10 million billion total: ~10% of body weight.
If you search online for the number of mitochondria or number of cells in the body, you’ll come up with a variety of statements by scientists on calculated estimates that serve to highlight the importance of keeping cellular structures well nourished and health and functional.
This report by Dr. Sinatra titled Metabolic Cardiology: The Missing link in Cardiovascular Disease, helps clarify importance of and the complexity of the mitochondrial function. Be sure to read the entire report. (8)
The importance of supporting energy production in heart cells
and the preservation of the mitochondria in these cells will be
the focus of a new frontier in cardiovascular prevention, treat-
ment, and management. Many physicians are not trained to
look at heart disease in terms of cellular biochemistry; there-
fore, the challenge in any metabolic cardiology discussion is in
taking the conversation from the “bench to the bedside.” An
understanding of the vital role that adenosine triphosphate
(ATP) plays in the heart is critical for any physician or clinician
considering therapeutic options that support ATP production
and turnover in jeopardized cardiac muscle cells.
Metabolic therapies that help cardiomyocytes meet their
absolute need for ATP fulfill a major clinical challenge of pre-
serving pulsatile cardiac function while maintaining cell and
tissue viability. D-ribose, L-carnitine, and coenzyme Q10 work
in synergy to help the ischemic or hypoxic heart preserve its
energy charge.
This article introduces how ATP, diastolic heart function, and
metabolic support help maintain cardiac energy by preserving
ATP substrates. Part 2 will investigate an in-depth biochemical
discussion of congestive heart failure with physiologic,
pathophysiologic, and treatment considerations.
(Altern Ther Health Med. 2009;15(2):48-50.)
Clips from this report:
The acute or chronic loss of energy substrates, mitochondrial dysfunction, and disruption of normal energy utilization and supply create conditions of reversible changes in the cell’s biochemical state. Four theories have been advanced that relate to the biochemical changes contributing to the pathology of cardiac disease: (1) a critical energy loss, (2) a critical accumulation of cellular calcium (3) the effects of free radical formation and (4) injurious effects of the accumulation of long-chain acyl compounds.
Clearly, a metabolic approach that derives enzymatic reactions in a preferential direction helps to support and restore the vulnerable heart. Such biochemical/metabolic interventions that improve energy metabolism in heart cells will offer the clinician new and exciting treatment options for patients at risk for cardiovascular disease, as well as for patients at any stage of the disease. Once an appreciation of how ATP repairs and restores heart cells is realized, targeted biochemical interventions to support ATP production and turnover will be embellished by physicians.[[/i]/size]
IV. Nutritional Support
Coenzyme Q10
“Coenzyme Q10 is probably the most widely used cofactor for treating mitochondrial-related diseases. CoQ10 functions as an electron carrier in the inner mitochondrial membrane, transferring electrons from complexes l and ll to complex lll. In addition to increasing biosynthesis of ATP (universal energy molecule), and acting as a potent free- radical scavenger, CoQ10 also reduces lactic acid levels, improves muscle strength and decreases muscle fatigability.” (9a)
There’s a variety of potentials, but fundamental to the whole process is the fact that to be fully functional, muscle tissue… be it skeletal or cardiac…needs a fuel source in the Kreb’s cycle to produce ATP or Adenosine 5’-tri-phosphate (ATP). And in order for ATP to be produced efficiently and in the quantity required to meet the body’s ATP production requirements for the Kreb’s cycle where Coenzyme Q10 or ubiquinone is utilized, the raw materials have to be available. CoQ10 is a core nutrient for the ATP production as well as the additional function as an antioxidant. CoQ10 is available from some foods but in very small amounts compared to the body’s requirements as well as how much additional is needed to for the antioxidant function to quell the oxidative damage. Aging creates more demand as does a high-energy output such as endurance exercise.
The pioneer researchers on the function of Coenzyme Q10 which is the core nutrient of mitochondria to produce the energy molecule ATP for heart failure include Prof. Frederick Crane, Drs. Karl Folkers, William Judy, Per Langsjoen, Peter Langsjoen, Gian Paolo Littarru - just a few of many and date back to 1957 when Dr. Crane isolated CoQ10 from beef hearts. There’s a brief historical chronology at footnote 9b. Years later in 1995, Italian researcher and Medical Doctor, Gian Paolo Littarru, wrote Energy and Defense, a slim, illustrated masterpiece of “Facts and perspectives on CoEnzyme Q10 in biology and medicine.” It’s a wealth of information in just 85 pages and 129 study references. Dr. Littaru is a prolific researcher participating in 141 studies listed Pub Med alone. Be sure to check the additional links
Reference 9c.
Note: For current CoQ10 supplement discussions, be aware of the ongoing marketing controversy over the form. In Reference 9 b, I’ve included the web link to a report by William V. Judy, PhD, leading CoQ researcher titled, “Coenzyme Q10 Facts or Fabrications” that helps clarify the claims for the ubiquinone form versus the ubiquinol form. At least 10 years ago, Alan R. Gaby, MD, said in a webinar on CoQ10 that the original version… the Ubiquinone (oxidized form) worked well and he didn’t see justification for spending 10 times that much for the reduced form, Ubiquinol. So, I’ve provided the Facts/Fabrications piece for support as well. There are numerous reports and various studies that say the ‘nol’ form is found to be more effective. So, FYI and be aware. The main point is to take enough. Some doctors say, “take as much as you can afford.”
Statins Deplete CoQ10 - Even though CoQ10 is available in some foods, the majority of CoQ10 is biosynthesized from other nutrients in the body. Although CoQ10 is naturally produced, a person may become unable to make the needed amount of CoQ10 due to aging, neurological disorders, cardiovascular disease, diabetes mellitus, certain cancers, gum disease, and the use of a “statin” or anthracycline medication. Since CoQ10’s discovery in 1957, it has become evident that many people develop deficiencies of this naturally-occurring nutrient. Deficiencies of CoQ10 are found in older individuals, people with neurological disorders or cardiovascular disease, and in people who are taking a “statin” cholesterol lowering drug or anthracycline medication. Source: 2008 ProThera product info bulletin
Additional mitochondrial support nutrients
Following is a list of additional nutrients known to enhance bioenergetic pathways within the mitochondria, prevent intra-mitochondrial free radical activity and maintain cell membrane integrity and fluidity…including the Krebs cycle and the electron transport chain. One notation indicated the combination of various supportive nutrients may benefit mitochondrial genetic mutations, either in-borne or acquired during aging or due to excessive exercise (such as mitochondrial myopathy) (9d)
One relatively new and popular substance is pyrroloquinoline quinone (PQQ), a water-soluble, vitamin-like compound designed to help support optimal mitochondrial biogenesis, which is critical for the promotion of healthy aging, optimal energy production, and protection from reactive oxygen species (oxidative stress). PQQ is a water-soluble, vitamin-like compound and an enzyme cofactor possessing antioxidative, neuroprotective, and cardioprotective properties that encourage mitochondrial biogenesis. [The product I use from Designs for Health (MitoPQQ) includes Rhodiola rosea that helps support the adrenal glands.] Research shows that Rhodiola rosea is a powerful herb for enhancing mitochondrial energy production and helps defend against free radicals in the nervous system as well as the mitochondria. Life Extension magazine offers reports on the PQQ in their product line.
There are several combination products which I like to call a ‘multi’ for mito health… One is Mitochondrial NRG ™ by Designs for Health and another is MitoThera(TM) by Klaire Labs, Life Extension offers Mitochondrial Basics with PQQ, and Researched Nutritionals offers ATP Fuel for mitochondrial/Kreb’s cycle support that includes NT Factors for cell membrane support.
Additional Mito Support Nutrients:
Acetyl L-Carnitine: Supports energy production and membrane function
Quercetin: Protects mitochondria against lipid peroxidation
Magnesium: Crucial to ATP production
Creatine: Helps maintain ATP levels
Alpha-lipoic Acid: Supports mitochondrial enzymes and extends antioxidant protection
Red Grape Extract: Potent antioxidant activity
N-Acetyl-L-cysteine: Counteracts cellular stress
Lecithin/Phosphatidylcholine: Maintains membrane fluidity
Malic Acid and Succinic Acid: for refilling of key Krebs cycle intermediates
Taurine to protect against differing types of free radicals both inside and outside of cells
Pantethine – needed to shuttle fats from blood stream across cellular membrane for entry
L-Carnitine – necessary to shuttle those same fats across the mitochondrial membranes for brning
B-vitamins, magnesium and manganese – required as Krebs cycle enzyme cofactors
Ribose – a nucleotide repleter and direct cellular energy source
Resveratrol and Curcumin – botanicals shown to induce the production of additional mitochondria (biogenesis) through SIRT1 gene signaling and PGC-1-alpha induction
V. Lipid Replacement Therapy
And, lastly: No report on mitochondrial support would be complete without addressing the very important research findings by Garth Nicholson, PhD, and Rita Ellithorpe, MD, on Lipid Replacement Therapy.
Lipid Replacement and Antioxidant Nutritional Therapy for Restoring Mitochondrial Function and Reducing Fatigue in Chronic Fatigue Syndrome and other Fatiguing Illnesses*
Garth L. Nicolson, Ph.D. and Rita Ellithorpe, M.D.
The Institute for Molecular Medicine, Huntington Beach, California, USA
Journal of Chronic Fatigue Syndrome 2006; 13(1): 57-68.
[www.immed.org]
How to Repair Mitochondria with Lipid Replacement
[thequantifiedbody.net]
Mitochondrial Dysfunction and Chronic Disease: Treatment With Natural Supplements
Garth L. Nicolson, PhD Integr Med (Encinitas). 2014 Aug; 13(4): 35–43. PMCID: PMC4566449 PMID: 26770107 [www.ncbi.nlm.nih.gov]
Membranes in Motion – The Fluid Mosaic Membrane Model (about mitochondrial membrane)
[www.clinicaleducation.org]
August 2012 - “ When mitochondrial cardiolipin and, to a lesser degree, other phosphatidyl phospholipids are damaged by oxidants, the chemical/electrical potential across the inner mitochondrial membrane is altered due to an increasingly “leaky” membrane that allows protons and ions to move across the membrane. This occurs because the oxidized membrane phospholipids no longer form a tight ionic/electrical ‘seal’ or barrier. The loss of this ionic/electrical barrier has significant effects on a number of cellular properties, such as loss of transport and cellular energy, altered metabolism and even initiation of cell death.”
The introduction to this report begins by noting: It isn’t every newsletter issue that FOCUS has the privilege of featuring a scientist whose theory of a fundamental biological phenomenon is accepted throughout the biological and medical sciences as the standard textbook model. Such is the case with S. J. Singer’s and Garth Nicholson’s landmark theory of the Fluid Mosaic Model of cell membranes. This model, proposed in 1972 and published in the prestigious journal SCIENCE, has been called a “unified theory” of the cell membrane. This model has been tested and retested for many decades, and is now believed to accurately predict the structure and behavior of all cellular membranes. Over the intervening years, this theory has been confirmed by many sophisticated physical and chemical techniques, including one known as freeze-fracture electron microscopy.
[www.clinicaleducation.org]
Why Lipid Replacement Therapy(LRT®) is Key to our Health
[www.clinicaleducation.org]
Lipid Replacement Therapy®, Fatigue and Dysbiosis – the Mitochondrial and Immune Connection
By Michael E. Ash BSc DO ND and Garth L. Nicolson, PhD 05 June 2012 [ra-infection-connection.com]
Reference 10 has an additional paper specific to mitochondria by Michael Ash, BSC, DO, ND DiplON…
Mitochondria and the Anti-Aging Role Of Lipid Replacement Therapies
Autophagy is initiated in response to cellular stresses such as nutrient starvation, oxidative stress, infection, or inflammatory stimuli. Targets of the selective autophagic machinery include organelles, protein aggregates, and even invading microorganisms. Mitochondria, which accrue damage as they age, can present a challenge to the cell through uncontrolled generation of reactive oxygen species (ROS) and become increasingly inefficient in their generation of adenosine tri-phosphate (ATP)
The selective removal of mitochondria by autophagy, known as mitophagy, is an important cellular adaptation to the challenge presented by this important organelle and the potential health hazard it represents. Equally important is the prevention of inappropriate damage and the related early repair of mitochondrial membranes to ensure that appropriate and time relevant mitophagy occurs. (10)
[[size=medium]b]VI. In Closing and Future Reflections[/b]
The intent of this post is to provide an overview and sampling of some of the many theories and practices that support the importance of healthy mitochondria for overall health including heart function as well as connecting the dots to that relating to arrhythmia. (An online search will provide more) and note that there are many very recent related studies.
This is longer than I intended. So, apologies, but it was difficult to limit length with such an abundance of compelling information available to share. Lastly:
The 2013 presentation Mitochondrial Dysfunction and the Emerging “Mitochondrial Medicine” by Alex Vasquez, D, ND, DO FACN… is an important observation worth reading as it upgrades many former philosophies and practices. The point Dr. Vasquez makes on inflammation and mitochondrial function is important… ( p. 22 of the pdf download at the link below)
Integrative Medicine • Vol. 12, No. 4 • August 2013 p 22 Vasquez—Viewpoints
Dr Vasquez:
Per my description of various inflammatory diseases in my “functional inflammology protocol,” I distinguish the three major categories of sustained/chronic inflammation as (1) metabolic, (2) allergic, and (3) auto-immune. In truth, the delineation of these categories is perceptual and conceptual rather than actual, given that significant overlap exists between states of metabolic, allergic, and autoimmune inflammation. Mitochondrial dysfunction plays a role within each of these subcategories of clinical disease.
Some of the simplest truths we can articulate to describe this landscape are (1) mitochondrial dysfunction causes inflammation, and inflammation causes mitochondrial dysfunction; (2) mitochondrial dysfunction increases free radical generation, and increased free radical generation promotes mitochondrial dysfunction via several mechanisms; and also that (3) nutrient deficiencies promote mitochondrial dysfunction, and the reverse is also true.
Lastly, in introducing the connection between inflammation and mitochondrial dysfunction, we can note that some of the so-called anti-inflammatory drugs—including the prototype prednisone—actually cause/exacerbate mitochondrial dysfunction. Thus in this situation we note the following paradox: A drug used in the treatment of inflammatory/allergic/autoimmune diseases could actually promote the same diseases via pharmaceutical-iatrogenic induction of mitochondrial dysfunction. End quote.
[www.academia.edu]
And… for a deeper dive into current philosophies regarding fundamental biophysics and mitochondrial function, check out Neurosurgeon, Jack Kruse, MD’s website at the links in Reference 11.
Once again, healthy regards (and healthy mitochondria) to all!
Jackie
VII. References and additional resource links
1. MitoQ.com
2. Kreb’s cycle… [www.cureffi.org]
Maximizing Your Body’s Performance by Ward Dean, MD and Jim English… note segment on Kreb’s cycle. [nutritionreview.org]
3. Connections to Oxidative Stress Damage and Arrhythmia + much more with an online search of those words. Here’s a start – see additional links after Ref. 10.
Understanding Oxidative Stress [www.wallerwellness.com]
Calcium and ROS: A mutual interplay Redox Biology Volume 6, December 2015, Pages 260-271
[doi.org] [www.sciencedirect.com]
Dysfunctional calcium load and oxidative stress via mitochondria and ER has been associated with myocardial infarction and other ischemic diseases. Consequently, cardiomyocytes develop hypertrophy, fibrosis, apoptosis, inflammation and structural cardiac remodeling eventually leading to cardiomyopathy and even heart failure [32]. In the aging heart, increased mitochondrial ROS result in thiol-oxidation of RyR channel hyperactivity and shortened refractoriness of Ca2+ release in cardiomyocytes. This mechanism probably plays an important role in the increased incidence of arrhythmias and sudden death in the ageing population [37].
Mitochondria and Arrhythmias
Free Radic Biol Med. Author manuscript; available in PMC 2015 Jun 1.
Kai-Chien Yang,a Marcelo G. Bonini,a,c,d and Samuel C. Dudley, Jr.* Free Radic Biol Med. 2014 Jun; 71: 351–361. Published online 2014 Apr 5. doi: [10.1016/j.freeradbiomed.2014.03.033] PMCID: PMC4096785 NIHMSID: NIHMS584382 PMID: 24713422
Abstract Mitochondria are essential to providing ATP thereby satisfying the energy demand of the incessant electrical activity and contractile action of cardiac muscle. Emerging evidence indicates that mitochondrial dysfunction can adversely impact cardiac electrical functioning by impairing the intracellular ion homeostasis and membrane excitability through reduced ATP production and excessive reactive oxidative species (ROS) generation, resulting in increased propensity to cardiac arrhythmias. In this review, the molecular mechanisms linking mitochondrial dysfunction to cardiac arrhythmias are discussed with an emphasis on the impact of increased mitochondrial ROS on the cardiac ion channels and transporters that are critical to maintaining normal electromechanical functioning of the cardiomyocytes. The potential of using mitochondria-targeted antioxidants as a novel anti-arrhythmia therapy is highlighted.
Mitochondrial oxidative stress promotes atrial fibrillation Wenjun Xie,1,* Gaetano Santulli,1,* Steven R. Reiken,1 Qi Yuan,1 Brent W. Osborne,1 Bi-Xing Chen,1 and Andrew R. Marksa,1,2
Sci Rep. 2015; 5: 11427. Published online 2015 Jul 14. doi: [10.1038/srep11427] PMCID: PMC4501003 PMID: 26169582
Redox modification of ryanodine receptors by mitochondria-derived reactive oxygen species contributes to aberrant Ca2+ handling in ageing rabbit hearts Physiol. 2013 Dec 1; 591(Pt 23): 5895–5911. Published online 2013 Sep 16. doi: [10.1113/jphysiol.2013.260521] [www.ncbi.nlm.nih.gov]
How mitochondria produce reactive oxygen species
Michael P. Murphy1 Biochem J. 2009 Jan 1; 417(Pt 1): 1–13.
Published online 2008 Dec 12. doi: [10.1042/BJ20081386]
PMCID: PMC2605959PMID: 19061483
[www.ncbi.nlm.nih.gov]
Oxidative stress: A possible pathogenesis of atrial fibrillation Medical Hypotheses Volume 72, Issue 4, April 2009, Pages 466-467 Cong-xinHuanga YuLiuaWen-fangXiabYan-hongTangaHeHuanga [doi.org] [www.sciencedirect.com]
Cellular and Molecular Mechanisms of Arrhythmia by Oxidative Stress Ali A. Sovari * Cardiol Res Pract. 2016; 2016: 9656078. Published online 2016 Feb 15. doi: [10.1155/2016/9656078 PMCID: PMC4770129 PMID: 26981310
4. The Wallace references… several… (First download the 1997 paper for a classic, foundational overview).
DOUGLAS C. WALLACE is Robert W. Woodruff Professor of Molecular Genetics and director of the Center for Molecular Medicine at the Emory University School of Medicine. He received his Ph.D. in microbiology and
human genetics from Yale University , where he and his collaborators first demonstrated that mitochondrial DNA
in human cells could encode heritable traits. Wallace has received many awards for his research on the human mitochondrial genome, including the 1994 American Society of Human Genetics’s William Allan Award for Outstanding Contributions to Human Genetics.
Mitochondrial DNA in Aging and Disease by Douglas C. Wallace (this is the classic 1997 paper)
….Defects in DNA outside the chromosomes— in cell structures called mitochondria can cause an array of disorders, perhaps including many that debilitate the elderly
Scientific American August 1007 pdf file.
[www.physics.ohio-state.edu]
Blog www.mitoaction.org/blog/wallace-mitochondrial-genetics-and-disease
Douglas Wallace, PhD won the 2017 Dr. Paul Jansen prestigious Award for Biomedical Research for his pioneering work in the field of mitochondrial genetics.
[mitochondrialdiseasenews.com]
Mitochondrial DNA in aging and disease (book) by Douglas C. Wallace (1997) [www.worldcat.org]
A mitochondrial bioenergetic etiology of disease Douglas C. Wallace J Clin Invest. 2013 Apr 1; 123(4): 1405–1412. Published online 2013 Apr 1. doi: [10.1172/JCI61398] PMCID: PMC3614529 PMID: 23543062
5. Myopathy
As an introduction, (Step 1) - check the following link for definitions of myopathy. Scan through them so you know the basics describing the condition. Here’s one of many myopathy definitions.
Source: www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/.../myopathy/
…. “Myopathy refers to a clinical disorder of the skeletal muscles. Abnormalities of muscle cell structure and metabolism lead to various patterns of weakness and dysfunction. In some cases, the pathology extends to involve cardiac muscle fibers, resulting in a hypertrophic or dilated cardiomyopathy.” [www.clevelandclinicmeded.com]
6. Mark Hyman, MD 7 keys to Ultrawellness [drhyman.com]
What the Heck are Mitochondria? Mark Hyman, MD
[drhyman.com]
Over Half the U.S. Population is Deficient in This Critical Mineral: Maximizing Your Mitochondria with Magnesium Part 1 Mark Hyman MD - [blog.wellnessfx.com]
UltraWellness Lesson 6: Energy, Mitochondria, and Oxidative Stress - Mark Hyman, MD [drhyman.com]
Dr. Hyman tells his personal story about toxins damaging his mitochondria.
[experiencelife.com]
7. David M. Brady, ND, DC, CCN,DACBN [drdavidbrady.com]
8. What are Mitochondria? Source: Integrative Cardiologist, Stephen Sinatra [heartmdinstitute.com]
Metabolic Cardiology: The Missing link in Cardiovascular Disease,
Stephen T. Sinatra, MD, FACC, FACN
[2cjz4t37rndy1lvklpf0rv9t-wpengine.netdna-ssl.com] (Part 1)
The Coenzyme Q10 Phenomenon by Stephen T. Sinatra MD, FACC, FACN
[www.goodreads.com]
Hardcover 1998
Coenzyme Q10 Benefits, Stephen Sinatra, MD
[heartmdinstitute.com]
9. Nutritional Support – Coenzyme Q10
9-a. Restoring Mitochondrial Function and Bio-energetics, Vitamin Research Products 2005, by Ward Dean MD – Reprinted @ [www.worldwidehealthcenter.net] Oct. 2016 Reference 1 – Cohen B. Gold D. Mitochondrial cytopathy in adults: What we know so far. Cleveland Clinic J. Medicine 2001 68:7, 625
Start here and scroll down to Series Four on Mitochondrial Function by Ward Dean MD for the historical background/history and views on mito function… from early 2000’s. [warddeanmd.com]
[warddeanmd.com]
Mitochondrial energy metabolism and ageing Volume 1797, Issues 6–7, June–July 2010, Pages 961-967 [www.sciencedirect.com]
9.b Coenzyme Q10 Facts or Fabrications, 2007, William V. Judy, PhD. [vitexnutrition.com]
Summary version by another website: [icqaproject.org]
This well-referenced 2010 Life Extension report “Reverse Mitochondrial Damage” offers rebuttal info on the CoQ10 forms as well as other supportive nutrient information. [www.lifeextension.com]
First drug to significantly improve heart failure mortality in over a decade
European Society of Cardiology (ESC) May 25, 2013
Summary: Coenzyme Q10 decreases all cause mortality by half, according to new results. It is the first drug to improve heart failure mortality in over a decade and should be added to standard treatment, according to experts. [www.sciencedaily.com]
9.c Good source for reference reading: [www.sciencedirect.com]
PubMed- Littarru studies [www.ncbi.nlm.nih.gov]
9. d Mito-Thera™ - Comprehensive Nutritional Support for Mitochondrial Energy Production – Spring 2010 and Mitochondrial NRG ™ supplement by Designs for Health product data sheet.
10. Mitochondria and the Anti-Aging Role Of Lipid Replacement Therapies
by Michael Ash BSc. DO. ND DipION0.
[www.clinicaleducation.org]
Mitochondrial Dysfunction and Susceptibility to Atrial Fibrillation in the Elderly
[physicianupdate.wordpress.com]
The path from mitochondrial ROS to aging runs through the mitochondrial permeability transition pore [www.researchgate.net]
Oxidative damage to mitochondrial DNA in atrial muscle of patients with atrial fibrillation Free Radical Biology and Medicine Volume 35, Issue 10, 15 November 2003, Pages 1310-1318 [doi.org] Po-HanLin*†Shih-HuangLee‡§Chia-PingSu*Yau-HueiWei*§
Exercise-induced protection against reperfusion arrhythmia involves stabilization of mitochondrial energetics. Am J Physiol Heart Circ Physiol. 2016 May 15;310(10):H1360-70. doi: 10.1152/ajpheart.00858.2015. Epub 2016 Mar 4. Alleman RJ1, Tsang AM1, Ryan TE1, Patteson DJ1, McClung JM1, Spangenburg EE1, Shaikh SR2, Neufer PD1, Brown DA3.
Oxidative Stress and Atrial Fibrillation - Finding a Missing Piece to the Puzzle One possible explanation for the limitations of current therapies is that they do not address effectively or completely the underlying causes of AF. Evidence has been mounting that AF is associated with systemic and cardiac oxidation.4,5 Kai-Chien Yang and Samuel C. DudleyJr Originally published12 Sep 2013Circulation. 2013;128:1724–1726
Cellular and Molecular Mechanisms of Arrhythmia by Oxidative Stress Ali A. Sovari Review Article Cardiology Research and Practice Volume 2016, Article ID 9656078, 7 pages [dx.doi.org]
Abstract Current therapies for arrhythmia using ion channel blockade, catheter ablation, or an implantable cardioverter defibrillator have limitations, and it is important to search for new antiarrhythmic therapeutic targets. Both atrial fibrillation and heart failure, a condition with increased arrhythmic risk, are associated with excess amount of reactive oxygen species (ROS). There are several possible ways for ROS to induce arrhythmia. ROS can cause focal activity and reentry. ROS alter multiple cardiac ionic currents. ROS promote cardiac fibrosis and impair gap junction function, resulting in reduced myocyte coupling and facilitation of reentry. In order to design effective antioxidant drugs for treatment of arrhythmia, it is essential to explore the molecular mechanisms by which ROS exert these arrhythmic effects. Activation of Ca2+/CaM-dependent kinase II, c-Src tyrosine kinase, protein kinase C, and abnormal splicing of cardiac sodium channels are among the recently discovered molecular mechanisms of ROS-induced arrhythmia.
Oxidative stress and inflammation as central mediators of atrial fibrillation in obesity and diabetes Cardiovascular Diabetology 201716:120 Basil S. Karam, Alejandro Chavez-Moreno, Wonjoon Koh, Joseph G. Akar and Fadi G. Akar [doi.org]
Mitochondrial Bioenergetics During Ischemia and Reperfusion.
Adv Exp Med Biol. 2017;982:141-167. doi: 10.1007/978-3-319-55330-6_8.
Consolini AE1, Ragone MI2,3, Bonazzola P3,4, Colareda GA5.
Oxidative stress in atrial fibrillation: An emerging role of NADPH oxidase Ji-jounYounabJunZhangabYixuanZhangabHouzaoChencDepeiLiucPeipeiPingdJames N.WeisseHuaCaiab Journal of Molecular and Cellular Cardiology Volume 62, September 2013, Pages 72-79 [doi.org]
Mitochondrial dysfunction and molecular pathways of disease
Steve R. Pieczenik, John Neustadt, ND Received 30 August 2006
[nbihealth.com]
11. Neurosurgeon, Jack Kruse, MD.
[jackkruse.com] [jackkruse.com]
[jackkruse.com]
[healthcastnow.libsyn.com]
|
Re: Mitochondrial Function - Oxidative damage, Aging, Arrhythmia and more December 11, 2018 03:57PM |
Registered: 10 years ago Posts: 1,748 |
Jackie:
Great piece of work, lots to read and learn. I do have a comment however over something that puzzles me.
You said;
"Lastly, in introducing the connection between inflammation and mitochondrial dysfunction, we can note that some of the so-called anti-inflammatory drugs—including the prototype prednisone—actually cause/exacerbate mitochondrial dysfunction."
Dr. Brownstein told me I could take this drug for the rest of my life without harm, I had hurt my shoulder and he said to take prednisone. Also, Shannon had a long favorable post about prednisone, I couldn't find that post maybe someone else can.
liz
Great piece of work, lots to read and learn. I do have a comment however over something that puzzles me.
You said;
"Lastly, in introducing the connection between inflammation and mitochondrial dysfunction, we can note that some of the so-called anti-inflammatory drugs—including the prototype prednisone—actually cause/exacerbate mitochondrial dysfunction."
Dr. Brownstein told me I could take this drug for the rest of my life without harm, I had hurt my shoulder and he said to take prednisone. Also, Shannon had a long favorable post about prednisone, I couldn't find that post maybe someone else can.
liz
|
Re: Mitochondrial Function - Oxidative damage, Aging, Arrhythmia and more December 11, 2018 05:34PM |
Registered: 6 years ago Posts: 819 |
Jackie, thank you for all the work compiling all this excellent information!
I may have missed something but the theory of getting lots and lots of anti-oxidants needs to be clarified?
According to what i've gleaned from this link : [www.sbs.com.au]
(it's an Australian public broadcaster and signing on is safe, they are not asking for money and suppose the registration is for their own data and for funding arguments with the government).
Antioxidants in supplement form is not efficacious nor helpful according to the researchers in that program. Suspect lots of anti-oxidants in food form would be - it wasn't investigated.
Let's not forget the importance of regular fasting periods. Dr. Valter Longo seems credible source of info there. We do know the importance of cell apoptosis, autophagy etc and how it is facilitated by fasting.
I may have missed something but the theory of getting lots and lots of anti-oxidants needs to be clarified?
According to what i've gleaned from this link : [www.sbs.com.au]
(it's an Australian public broadcaster and signing on is safe, they are not asking for money and suppose the registration is for their own data and for funding arguments with the government).
Antioxidants in supplement form is not efficacious nor helpful according to the researchers in that program. Suspect lots of anti-oxidants in food form would be - it wasn't investigated.
Let's not forget the importance of regular fasting periods. Dr. Valter Longo seems credible source of info there. We do know the importance of cell apoptosis, autophagy etc and how it is facilitated by fasting.
|
Re: Mitochondrial Function - Oxidative damage, Aging, Arrhythmia and more December 11, 2018 09:56PM |
Registered: 11 years ago Posts: 4,220 |
Jackie,
Great job, thanks!
Here is a podcast with Dr. Doug Wallace. He is the guy that figured out that mitochondrial DNA are only inherited from the mother - the egg destroys the male mitochondrial DNA. That might be enough to earn him a Nobel Prize someday.
Why? Well it turns out that the most energy is produced when all the mito DNA are the same. The more divergence, the less energy. Less energy = more illness. With the same nuclear DNA, the more the divergence ("heteroplasmy") you get different disease phenotypes (more severe). Heteroplasmy can increase over time, due to age, genetic or environmental factors.
<[www.ihmc.us]
Here is a presentation he gave in 2015 <[www.youtube.com]
George
Edited 2 time(s). Last edit at 12/11/2018 09:59PM by GeorgeN.
Great job, thanks!
Here is a podcast with Dr. Doug Wallace. He is the guy that figured out that mitochondrial DNA are only inherited from the mother - the egg destroys the male mitochondrial DNA. That might be enough to earn him a Nobel Prize someday.
Why? Well it turns out that the most energy is produced when all the mito DNA are the same. The more divergence, the less energy. Less energy = more illness. With the same nuclear DNA, the more the divergence ("heteroplasmy") you get different disease phenotypes (more severe). Heteroplasmy can increase over time, due to age, genetic or environmental factors.
<[www.ihmc.us]
Here is a presentation he gave in 2015 <[www.youtube.com]
George
Edited 2 time(s). Last edit at 12/11/2018 09:59PM by GeorgeN.
|
Re: Mitochondrial Function - Oxidative damage, Aging, Arrhythmia and more December 12, 2018 09:14AM |
Registered: 6 years ago Posts: 18,881 |
Thanks, Liz, George and Joe.
Liz... the quote you mentioned was from Dr. Vasquez's observations.... not my personal view or statement....
as are the other observations regarding the need for optimizing antioxidants to suppress the oxidative stress damage.
I have just re-quoted some of the relevant points concerned why the oxidative stress damage is relevant for maintaining healthy mitochondria. An underlying factor, obviously, is that oxidative stress causes inflammation... and we all know the story about inflammation and thick, sticky blood, etc.
Thank you George for the current Wallace podcast. I'll be watching soon.
Jackie
Liz... the quote you mentioned was from Dr. Vasquez's observations.... not my personal view or statement....
as are the other observations regarding the need for optimizing antioxidants to suppress the oxidative stress damage.
I have just re-quoted some of the relevant points concerned why the oxidative stress damage is relevant for maintaining healthy mitochondria. An underlying factor, obviously, is that oxidative stress causes inflammation... and we all know the story about inflammation and thick, sticky blood, etc.
Thank you George for the current Wallace podcast. I'll be watching soon.
Jackie
|
Re: Mitochondrial Function - Oxidative damage, Aging, Arrhythmia and more February 28, 2019 11:00AM |
Registered: 10 years ago Posts: 31 |
Jackie, what a great, factual report on the mitochondria. Thanks so much for all you hard work in developing this summation.
The message I would like to convey here is SOME congestive heart failure is reversible. No doctor ever told me that. But I am living proof that it happens.
First of all, let me share that I have Afib with at least one food trigger, gluten sensitivity. Prior to having Maze surgery in 2007 in Chicago by Patrick McCarthy, MD, my ejection fraction was .17. Following surgery, 4 days later, my EF jumped to just under 50. Since 2007 I have had tremendous quality of life exerting myself as never before.
Flash forward - October 2017 - while drinking a kombucha health drink, I felt my heart was racing and immediately looked at the label to see it contained wheat/gluten. It didn't, but it did contain a large amount of caffeine. I NEVER drink caffeine and recognized I was in trouble, just couldn't tell how much.
At the time, I had just said "goodbye" to my cardiologist who knew my case well, and was waiting to me a new cardiologist who didn't know my case; nor does it practice integrative medicine. So I went home and took my PIP dosage (Pill in Pocket) which I use from time to stop any arrhythmia's from advancing. I did this for about 3 weeks, and one Sunday morning awakened with SOB and headed to ER where the blood work PBNP was 3248 indicating heart failure. Sometime later the did another PBNP and it was 3915. Normal for my age is in the 200's. And this is when I rec'd the new I was in Congestive Heart Failure. I was sent home with a low dose beta blocker, high blood pressure med, and diuretic.
With lots of time to think over my situation and how I got there, I recalled a book that was recommended by my previous cardiologist that I had never thoroughly read by Stephen Sinatra, MD. I devoured the book when I realized it addresses Congestive Heart Failure and set myself up with a dosage schedule of what to take when, ordered his latest book, and recommended supplements.
I started the Sinatra program.
April 2018 - SOB and entered ER again and they couldn't find anything wrong. I asked for a retest of the PBNP and the new test was 219 which is the normal age for anyone my age. My beta blocker dose was cut back 50% and the SOB subsided.
With that good news I gently pressed forward to resume my regular exercise program. Last summer I was still working up to walking 4 miles a day, but cycled 525 miles for the year riding until it became too cold.
Sinatra's program works! Even if I wouldn't have fully recovered, I am convinced I could have moved up on the scale to having more quality living unless, of course, I was at Level 4 and that's probably debatable.
SInatra's program is all about addresses the mitochondria. I really, really learned a lot about keep the mito's throughout the body healthy. Heal the mito's heal the body.
Hope this is helpful. I have learned so much from this group of Affibers who are incredibly bright and willing to take time to share what works.
Again, thanks Jackie for all your hard work.
Lois
Edited 2 time(s). Last edit at 03/05/2019 08:59AM by LSulka.
The message I would like to convey here is SOME congestive heart failure is reversible. No doctor ever told me that. But I am living proof that it happens.
First of all, let me share that I have Afib with at least one food trigger, gluten sensitivity. Prior to having Maze surgery in 2007 in Chicago by Patrick McCarthy, MD, my ejection fraction was .17. Following surgery, 4 days later, my EF jumped to just under 50. Since 2007 I have had tremendous quality of life exerting myself as never before.
Flash forward - October 2017 - while drinking a kombucha health drink, I felt my heart was racing and immediately looked at the label to see it contained wheat/gluten. It didn't, but it did contain a large amount of caffeine. I NEVER drink caffeine and recognized I was in trouble, just couldn't tell how much.
At the time, I had just said "goodbye" to my cardiologist who knew my case well, and was waiting to me a new cardiologist who didn't know my case; nor does it practice integrative medicine. So I went home and took my PIP dosage (Pill in Pocket) which I use from time to stop any arrhythmia's from advancing. I did this for about 3 weeks, and one Sunday morning awakened with SOB and headed to ER where the blood work PBNP was 3248 indicating heart failure. Sometime later the did another PBNP and it was 3915. Normal for my age is in the 200's. And this is when I rec'd the new I was in Congestive Heart Failure. I was sent home with a low dose beta blocker, high blood pressure med, and diuretic.
With lots of time to think over my situation and how I got there, I recalled a book that was recommended by my previous cardiologist that I had never thoroughly read by Stephen Sinatra, MD. I devoured the book when I realized it addresses Congestive Heart Failure and set myself up with a dosage schedule of what to take when, ordered his latest book, and recommended supplements.
I started the Sinatra program.
April 2018 - SOB and entered ER again and they couldn't find anything wrong. I asked for a retest of the PBNP and the new test was 219 which is the normal age for anyone my age. My beta blocker dose was cut back 50% and the SOB subsided.
With that good news I gently pressed forward to resume my regular exercise program. Last summer I was still working up to walking 4 miles a day, but cycled 525 miles for the year riding until it became too cold.
Sinatra's program works! Even if I wouldn't have fully recovered, I am convinced I could have moved up on the scale to having more quality living unless, of course, I was at Level 4 and that's probably debatable.
SInatra's program is all about addresses the mitochondria. I really, really learned a lot about keep the mito's throughout the body healthy. Heal the mito's heal the body.
Hope this is helpful. I have learned so much from this group of Affibers who are incredibly bright and willing to take time to share what works.
Again, thanks Jackie for all your hard work.
Lois
Edited 2 time(s). Last edit at 03/05/2019 08:59AM by LSulka.
|
Re: Mitochondrial Function - Oxidative damage, Aging, Arrhythmia and more March 04, 2019 04:40PM |
Registered: 6 years ago Posts: 18,881 |
Hi Lois - Good to hear from you...and Thanks for your news... glad you are doing so well. And thanks also for emphasizing the Sinatra program and also the importance of helping to keep the mitochondria healthy and functional.
Please list the Sinatra books for new readers.
Be well,
Jackie
Please list the Sinatra books for new readers.
Be well,
Jackie
|
Re: Mitochondrial Function - Oxidative damage, Aging, Arrhythmia and more March 04, 2019 05:54PM |
Registered: 10 years ago Posts: 31 |
Happy to do so, Jackie.
Stephen T. Sinatra, MD, FACC, FACN, CNS
Latest Book: The Sinatra Solution - Metabolic Cardiology
Dr. Sinatra's informational website
www.heartmdinstitute.com
Dr. Sinatra's heart and lots of great articles
Heart healthy vitamins, supplements and advice
www.drsinatra.com
Dr. Stephen Sinatra - Facebook
Foundation for Alternative & Integrative Medicine
This is a great website for information, latest findings, and articles by Dr. Sinatra and other experts
www.faim.org
Through the years I have always found "peace" when I find others who know more about Afib than I do. There's so much to learn and soooooo many people are walking around with it.....or will be at sometime. I learned so much from this group even though many may not be here anymore. We just want to keep the ball rolling...
Good Health to all,
Lois
Stephen T. Sinatra, MD, FACC, FACN, CNS
Latest Book: The Sinatra Solution - Metabolic Cardiology
Dr. Sinatra's informational website
www.heartmdinstitute.com
Dr. Sinatra's heart and lots of great articles
Heart healthy vitamins, supplements and advice
www.drsinatra.com
Dr. Stephen Sinatra - Facebook
Foundation for Alternative & Integrative Medicine
This is a great website for information, latest findings, and articles by Dr. Sinatra and other experts
www.faim.org
Through the years I have always found "peace" when I find others who know more about Afib than I do. There's so much to learn and soooooo many people are walking around with it.....or will be at sometime. I learned so much from this group even though many may not be here anymore. We just want to keep the ball rolling...
Good Health to all,
Lois
Sorry, only registered users may post in this forum.