In the last 3 blogs in this series we have looked at what the mitochondria is (part 1), how they affect the body when they are dysfunctional (part 2) and what actions can reduce the function of the mitochondria (part 3).

One of the most important supplements to use when mitochondria dysfunction is suspected in CoQ_10. It is usually at least 100 mg daily. We will investigate this in more detail later, but here I will say that the ubiquinol form is considered the best. Typically, it’s prescribed in combination with other nutrients, in what’s often called the “mitochondrial cocktail,” and a knowledgeable and progressive doctor might recommend some or all these supplements: creatine monohydrate, vitamin C, vitamin E, alpha – lipoic acid, thiamine (vitamin B1), riboflavin (B2), niacin (B3), L – carnitine, or L – arginine. Others include D – ribose, PQQ, magnesium, and medium – chain fatty acids (e.g. Krill), Cannabis, Ginseng and Medicinal Mushrooms. 

The Role of Mitochondria in Cardiovascular Disease 

Cardiovascular disease is a broad category of health conditions and is likely of great interest to the majority taking this course because it is one of the leading causes of death on the planet. Cardiac symptoms in MD are very common. 

Dysrhythmias: With poor energy delivery at the cellular level there may be disturbance of the heart’s electrical conductivity, which causes dysrhythmias.

Conditions such as angina, hypertension, congestive heart failure, ischemia, and diastolic dysfunction all have their root in MD. Not only can it be the cause of the problem it can prolong issue related to them making them more long-term and chronic. Interestingly, when purine building blocks of ATP leak from the cells, they are metabolized to uric acid, and high uric acid in patients is often reflective of dysfunctional ATP metabolism (an important point to understand for clinicians treating gout, for example).

Chest pain (angina): Again, with poor energy delivery the same problem occurs in heart muscle as skeletal muscle. This muscle pain is due to poor energy. However, in MD or CFS it is often not diagnosed as such because typically angina clears quickly with rest, where energy delivery is impaired because of poor mitochondrial function. All the high energy demands of the heart must be met by a small pool of ATP. As a result, the ATP supply must be continuously replenished — and again, that is the job of our mitochondria.

Low blood pressure: Poor energy supply to cardiac muscle means that the muscle cannot contract powerfully and the heart becomes a weak pump, this manifests with low blood pressure. This low cardiac output can almost be considered bordering on heart failure. Often this is followed by the panic hormone adrenaline (epinephrine) which may cause palpitations.

PoTS:  Postural tachycardia syndrome is an abnormal increase in heart rate that occurs after sitting up or standing. Some typical symptoms include dizziness and fainting. It’s sometimes known as postural orthostatic tachycardia syndrome. It is much easier to pump blood on the horizontal, so CFS sufferers feel better lying down. (Actually, we all feel more rested lying down and do such to sleep, of course.) Often to compensate for this the heart beats faster, which of course uses more energy, thus depleting mitochondria function more. This is often blamed on the autonomic nervous system but is most often a condition of MD. 

I’m hoping that by now you can appreciate the important role mitochondria have in one of the leading causes of death; but you’ll soon see that their importance goes far beyond the cardiovascular system and plays a crucial role in essentially every functional system in the body.

All the above problems compound all the other symptoms of MD. The heart delivers fuel and oxygen to all cells in the body and if fuel and oxygen delivery is impaired then this too further impairs energy delivery mechanisms (see Figure for further example of a vicious cycle).  

A 2-year, multicenter study of 420 patients with moderate to severe CHF showed that adding CoQ₁₀ (100 mg three times daily) to conventional drug therapy reduced CV mortality by 42% and all-cause mortality by 44%. It also reduced CHF-related hospitalizations.

Shortness of breath: If energy delivery at the cellular level is impaired, the brain may misinterpret this as poor oxygen delivery and stimulate the respiratory center to breathe harder. This in turn can cause a form of hyperventilation, which can even make the problem worse. This creation of another vicious circle of changing the blood to become more alkali so that oxygen sticks more acidly to hemoglobin thus making oxygen delivery poorer. 

Poor immune function and susceptibility to infections

The immune system is like the brain, being responsive to decision making and activity. This hugely energy demanding system can send a healthy person to bed within hours of a flu. Stress in one’s life can make a person more susceptible to disease, especially infections.

Poor liver function:

Intolerance of alcohol and drugs may result in the symptom of feeling poisoned. This is extremely common for alcohol and drugs in MD patients. Usually this is due to the liver already working at maximum capacity and doesn’t have extra energy to deal with additional foreign chemicals. 

Almost invariably MD sufferers struggle with: 

• Alcohol: This is consumed in gram amounts, 10 to 100 – fold higher than most prescription drugs. 
• Statins: They inhibit endogenous production of coenzyme Q10 and therefore energy delivery by mitochondria. 
• Beta blockers: They slow the heart and reduce cardiac output. 
• Antidepressants: Often only small doses can be tolerated without side effects – typically, one quarter or less of a normal therapeutic dose. 
• Poor gut function: This whole process of breaking down and absorbing nutrient require large amounts of energy. MD patient often have digestive symptoms often due to allergies and upper fermenting gut. 
• Poor hormonal function: the making of hormone require a fair amount of energy. This is further compounded by MD suffers often suppressing the hypothalamic pituitary adrenal (HPA) axis. Often there is a hypothyroid issue (low thyroid function) thrown in on the side. This of course deliverers low energy to the entire body.
• Poor renal function:  the kidneys are also greatly demanding of energy. They cannot tolerate even a temporary cut – back in energy without going into failure. So, they have evolved a protective series of hormones – renin-angiotensin system. This has evolved to help deliver energy to the kidney while it is failing in other areas of the body. 
• Loss of libido: this is Nature’s way of preventing procreation when there is no energy for such. The business of having babies, as any parent knows, is hugely demanding of energy – much more so for the women than the men, which I suspect is why women suffer this symptom much more than men.
• Physical degeneration including osteoporosis: this is a longer – term consequence of MD – part of the reason is simply that bones need exercise to keep them strong and MD sufferers cannot do such. Because of this we will have to rely mostly on supplementation to aid in reverse it  
• The Role of Mitochondria in the Nervous System, Brain, and Cognitive Health. The higher the demand for a tissue for energy, the more mitochondria are present. This means we will often see symptoms related to dysfunction in the central nervous system earliest. Since the nervous system consumes about 20% of the bodies energy, even though it only makes up 2% of the body mass. We will often find symptoms of energy loss from mitochondria dysfunction first.  
• Stroke: Suffocating the Brain Mitochondria.  The brain consumes approximately 14% of the body’s blood and 20% of the oxygen supply even though the brain’s energy reserves are actually very small. The brain’s metabolism can sustain energy production for only about one minute before it needs to be replenished. Meaning they are very vulnerable to ischemia (reduced blood flow) and lack of oxygen (hypoxia). This means as the oxygen runs out, the cell shift to anaerobic metabolism for a short time, but after a few minutes suffer from irreversible injuries. 

Mitochondrial Involvement in Neurodegeneration: As early as 1999 published studies corroborated the role of abnormal mitochondrial dynamics in neuronal cell death and the onset of Alzheimer’s, Parkinson’s, and Huntington’s disease and other neurodegenerative disorders. Although many health conditions, aging and general neurodegeneration have similar basic causes, the physiology of the brain is unique in certain ways, and its pathologies present some interesting mechanisms and features.

Problems with mitochondrial energy production and movement throughout neurons have been implicated in Alzheimer’s, Parkinson’s, ALS, and other major neurodegenerative diseases; this 2013 research adds a key piece of the puzzle and gives us more reason to target mitochondria and cellular energy in these illnesses.

Excitotoxicity: In the late 1980s, scientists at the National Institutes of Health proposed that excitotoxicity (toxicity from overstimulation of nerve cells) develops when the energy level of neurons declines. Subsequent research has confirmed this, as studies have shown that CoQ₁₀ protects against excitotoxicity by raising energy levels in nerve cells. 

The neurotransmitter glutamate normally transmits excitatory impulses. In neurodegeneration, however, the brain becomes chronically oversensitive to glutamate, which then becomes a slow acting “excitatory toxin” on brain cells. For mitochondria, this means that they are constantly under the direction to produce more energy—more energy than the neurons need. With this higher rate of activity comes a higher rate of free-radical production and, over time, comes the accelerated demise of these mitochondria. Ultimately, this chain of events results in dysfunction within the neurons. 

Mitochondria in Neuronal Signaling: Brain cells talk to one another in a variety of strengths or intensities. Sometimes they speak loud and clear, but other times they whisper or mumble. For years scientists questioned why and how neurons change their intensity so frequently. A study by Sun and colleagues published in the summer of 2013 showed that rapidly moving mitochondria emit bursts of energy, and this might regulate neuronal communication. 

Alzheimer’s Disease: Don’t Forget the Mitochondria!

An 80-year-old has about a 30% chance of having or developing Alzheimer’s. Even though the mechanism is quite complex and has not been worked out yet. At the cellular level there is extensive loss of neuron and there are high levels of insoluble fibrous deposits. The core of the deposit is a toxic protein called amyloid beta – the hallmark of Alzheimer’s – that attacks the cell on several fronts. However, there is evidence to suggest that the formation of amyloid beta is the brain’s way of defending against oxidative stress (a result of Alzheimer’s, not a cause). In her recent book, The Alzheimer’s Antidote, Amy Berger does an excellent job of assessing the current situation and offers diet and lifestyle – related solutions based on the newest information and research. Despite some seemingly contradictory studies and insights, Berger’s conclusion is that Alzheimer’s is a metabolic disorder. 

Parkinson’s Disease: Rethinking L – Dopa Therapy: Some recent research has suggested that CoQ₁₀ can protect the brain cell from toxicity, and thus reduce Parkinson’s Disease. Flint Beal, a prominent neurologist, has spent years proving that CoQ₁₀ has neuroprotective properties that might help diseases such as Parkinson’s and Huntington’s, and a growing body of scientific evidence supports his hypothesis. Research has established that mitochondria from platelets in patients with early, untreated Parkinson’s had reduced activities of Complexes I, II, and III (compared to age – matched controls).

Depression: Up to 20 percent of the population will experience some form of a stress – associated disease, including depression, yet despite decades of research, we still do not completely understand this complex brain disorder.

An increasing body of evidence implicates mitochondria in the etiology of depression. It has been proposed that the balance between stress response (the adaptation to our constantly changing environment) and available energy (our mitochondrial function) is crucial for mental health. More specifically, stress activates different areas of the brain, and changes its structure and function (what is called neuroplasticity). This comes at a metabolic cost, and of course, it’s the mitochondria that are responsible for meeting this additional energy demand. 

People with optimal mitochondrial function can cope with the energy demands of stress-induced neuroplasticity, which means that these individuals are at relatively low risk for depression. In individuals with mitochondrial dysfunction, on the other hand, stress-induced depletion of the brain’s energy supply could ultimately compromise neuroplasticity, which, in time, could render an individual vulnerable to clinical depression as the adaptation response falters. 

Attention-Deficit/Hyperactivity Disorder: Pay Attention to the Mitochondria 

Attention-deficit/hyperactivity disorder (ADHD) is a heterogeneous condition that affects a significant, and growing, proportion of the population. ADHD is defined by persisting, developmentally inappropriate, cross-situational, and impairing levels of inattention, impulsiveness, and hyperactivity. Several studies have linked ADHD with markers of elevated oxidative stress and free-radical damage, and increasing evidence also documents that ADHD is linked to environmental pollutants that are known to adversely affect mitochondria. Whether induced by pollutants, illness, or predisposing genetics, elevated free-radical damage and its effects upon mitochondria might be a significant factor in some—and potentially many—cases of ADHD. This indicates that treating mitochondrial dysfunction might be beneficial for some individuals who have ADHD. 

Chronic Fatigue Syndrome, Myalgic Encephalomyelitis, and Fibromyalgia 

Although chronic fatigue syndrome (CFS), myalgic encephalomyelitis (ME), and fibromyalgia are all distinct and separate conditions, due to their similarity and significant overlap in symptomatology, they often discuss together. The clinical picture of ME is as for CFS plus symptoms of inflammation. ME sufferers have ALL the above symptoms of poor energy delivery plus the symptoms of inflammation: infection, allergy and auto – immunity.

Type 2 Diabetes 

Commonly referred to as just diabetes, this metabolic disorder is characterized by high blood sugar over a prolonged period. If this form of metabolic syndrome is left untreated it often leads to cardiovascular diseases, neurological disorders, strokes, kidney failure and coma.

While the management of diabetes has come a long way, recent evidence suggesting mitochondrial dysfunction lies at the heart of this disorder has given us insight into how to stop its progression, and even reverse it! By working on the mitochondria, we can reduce problems and eventually rejuvenate the metabolic system.

Mitochondrial Damage in Type 2 Diabetes 

Recently, mitochondria have been identified as playing an important role in pathogenesis of type 2 diabetes, which act both on the release action of insulin at the target tissue.

The chain of events looks something like this: 

1. mitochondrial damage in the target cells, such as muscles, results in lipid accumulation 
2. lipid accumulation results in insulin resistance
3. due to insulin resistance, the beta cells in the pancreas must increase their metabolism to create more insulin (and then package it up, and secrete it—all of which takes energy) 
4. while this metabolism increase helps control blood sugar to some degree in the short term, over time these beta cells accumulate damage to their mitochondria due to chronically high metabolism and energetic demand; and finally 
5. the beta cells start to die off, resulting in a drop in insulin and a spike in blood glucose, which is what is typically seen in long-standing uncontrolled type 2 diabetes.

 

Mitochondrial Diabetes 

Typically presenting at middle age, mitochondrial diabetes is a form that originates from an mtDNA defect, so this diabetes is maternally transmitted and interestingly, often associated with hearing loss (particularly for high tones). Here we have decreased insulin secretion but not insulin resistance suggesting that it is a problem with the mitochondria in the beta cells of the pancreas.

Covid related Issues: Mitochondria appear to be important in COVID-19 pathogenesis because of its role in innate antiviral immunity, as well as inflammation. Few peculiarities of COVID-19 make it far more dangerous than other epidemics in the past caused by corona viruses namely, severe acute respiratory syndrome (SARS) of 2002 and middle east respiratory syndrome of 2012. 

Mitochondrial dysfunction in COVID-19 is an emerging and interesting topic. A better understanding of the role of mitochondria in COVID-19 may provide answers to the key perplexing questions.

Treating Mitochondrial Disease: Recent advances in medicine, science, and genetics have helped us gain a better understanding of the diagnosis and treatment of mitochondrial diseases. Unfortunately, there is still no cure, and current treatments cannot guarantee symptom relief or improvement in quality of life. The effectiveness of treatment varies depending on the exact disorder affecting a person and its severity. Case reports and pilot studies have found that some patients with mitochondrial diseases respond to long-term CoQ₁₀ therapy, and promising results have been reported in mitochondrial encephalomyopathy, lactic acidosis, and stroke like syndrome (MELAS); Kearns-Sayre syndrome; and maternally inherited diabetes with deafness. An Italian study of patients with mitochondrial disease measured the bioenergetic activity in their brain and skeletal muscles and demonstrated the positive impact of CoQ₁₀ therapy. After six months of CoQ₁₀ therapy (at only 150 milligrams daily), brain bioenergetics returned to normal in all patients, and skeletal muscle energetics improved significantly. Several other studies have also confirmed the value of CoQ₁₀ in mitochondrial disease.

In Part 5, our next and last section of this blog series, we are going to look at the role of supplementation and treatment for Mitochondria for the various health concerns.