I have spent an estimated 30,000 hours in research and implementation of therapies to resolve my issues, I went from being bedridden for 20 hours per day to have a near functional life. If anyone needs help, always feel free to contact me .
Chapter 4
Krebs Cycles
(Problem Starts Here)
All disease starts at the cellular level. When the energy at the cellular level is low then so are you.
There are trillions of cells in the body. Cells are the building blocks of everything, the foundation. They make up organs, tissues, immune cells and so on. Cells are individual or specialized, for instance, A cell in the eye does something different than the cell in your skin but for the most part they function similar. Cells are mini factories. Cells have a complex cycle that can be measured. Low energy equals cell dysfunction. Cell dysfunction can be caused by a number of factors.
The Krebs Cycle is named after the Nobel Prize Winner Dr. Hans Krebs. His work focused on the very complex chemical reactions that were performed in the cell.
Wikipedia defines the Krebs Cycle this way:
The citric acid cycle — also known as the tricarboxylic acid cycle (TCA cycle), or the Krebs cycle, are chemical reactions used by all aerobic organisms to generate energy through the oxidation of acetate derived from carbohydrates, fats and proteins into carbon dioxide and chemical energy in the form of adenosine triphosphate (ATP).
In addition, the cycle provides precursors of certain amino acids as well as the reducing agent NADH that is used in numerous other biochemical reactions. Its central importance to many biochemical pathways suggests that it was one of the earliest established components of cellular metabolism and may have originated abiogenically.
What does all this mean? It means that the cells depend on nutrients to perform their function and when they do not, the cycle does not work and when the cycle does not work then you feel that. You might feel that in your joints, your mood, your energy, your resistance to stress or resistance to infections and many other things.
The cells use a chemical pathway which can be similar to say your car. Your car depends on certain elements for the engine to run: gas, spark plugs, fuel injection system, engine management systems and so on. Take one of these out of the equation and your car will not run right or worse yet, will not start. Change some slight settings say on the spark plug gap and presto your car will not run or will not perform as expected.
The cells do specific things, for instance cells in pancreas may produce insulin, while other cells in the pancreas manufacture glucagon. cells both import and export things, for instance those cells producing insulin export that hormone to other cells which receive them. and that pancreas cell producing insulin received something from another cell.
Cells are dependent on nutrients to do their thing. Cells are damaged by oxidative stress.
Krebs Cycle Disruptors
The cycle can be disrupted by a number of things such as toxins, improper nutrition, pathogenic involvement, fallout from immune reactions and stress.
ATP - the energy producer NADH
ATP is considered the molecular unit of currency for energy meaning if you do not produce adequate amounts then you are at an energy deficiency.
Mitochondria
More press is being given to mitochondria due to a number of degenerative diseases which include a wide array of problems from neurological, muscular, energy production, auto-immune and many others.
The mitochondria are little factories inside the cell whose responsibility is to produce energy, studies show that mitochondria are damaged in M.E. patients. With damaged mitochondria comes lower energy which means resistance is lowered. A decrease in exercise ability is noted in M.E. patients and will increase oxidative stress which is not good. Reduced mitochondrial output also reduces immunity, endocrine outputs, brain function and resistance to disease. (3)
Most common literature found about mitochondrial disease miss the problem which is oxidative stress. Researchers find a clear link between oxidative stress and mitochondrial damage (4). The most likely causes of oxidative stress in the M.E. patient is immune activation caused by a pathogenic invasion. Toxins also created oxidative stress.
Krebs and M.E.
Dr. Bell has studied the role of the Kreb’s cycle in M.E. patients and Bell postulates that ME/CFS involves septic shock, beginning with a serious infection, the production of cytokines, an increase in nitric oxide, and ensuing problems with cellular energy production.
He believes that oxygen starvation occurs due to many factors which ultimately result in hyper-aroused immune response, hindering cellular production of ATP. Dr. Bell sees this as potentially the root cause of many ME/CFS symptoms.
What you can do
Talk to your doctor about improving your nutrition quality, avoid and detoxify toxins and address the pathogen issue if present.
Testing of Krebs Cycle
Genova and other labs offer Organic Acid testing which can isolate many of the parts of the Krebs Cycle to determine missing links. I did the test and measured a 132 of the citric acid cycle which range is 500-2000. If the output is low then your energy is low which leads to increased stress.
How this test helps
Helps confirm that a low Krebs cycle leads to dysregulation in the body. Identifies nutrient co-factors that might be deficient. Cons: The test is likely expensive and may not be an absolute in locating the problem.
Conclusion
When the cells are not completing the Krebs Cycle then you will not be well. The Krebs Cycle is dependent on raw materials to do their thing, the cycle can be interrupted by
Resources
Nutrition Review Kreb’s Cycle Intermediates Ward Dean, MD and Jim English
http://nutritionreview.org/2013/04/krebs-cycle-intermediates/
References
1/ Biochemistry. 5th edition.Berg JM, Tymoczko JL, Stryer L.
New York: W H Freeman; 2002. http://www.ncbi.nlm.nih.gov/books/NBK21163/
2/ Oxidative and Nitrosative Stress and Immune-Inflammatory Pathways in Patients with Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS)
Gerwyn Morris and Michael Maes
3/ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3964747/
4/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3184498/
Chapter 4a
The Cell Membrane
The cell membrane is the outer layer of the cell. It not only is the structure of the cell (holding the cell together) but serves as a portal for both chemicals coming in but also going out.
The membrane is made up by healthy fats and by proteins.
Purpose of the cell and the cell membrane
The purpose of the cell is many; cell signaling, production of chemicals that other cells use, the cell also it takes in raw materials to produce things.
Channelopathy
Channelopathy is suggested as explaining many symptoms in M.E. patients. The idea is that the membrane has channels (gates) that control many things, in this case they studied the roles of electrolytes. Electrolytes play key roles in human health including energy production, immunity and detoxification, just to name a few. The researchers found abnormal abilities of these channels.
Possible explanations of this defect included viral activity, genetic defects and the most likely, defects due to oxidative injury.
Phospholipids
Phospholipids are lipids (fats) and comprise the cell membrane. They can be found in many foods such as eggs, soy and other foods. The b vitamin choline plays a key role in the synthesis of phospholipids.
Cholesterol is important
Cholesterol is thought to be bad*, mainly due to the pharmaceutical marketers but cholesterol plays important roles in the body. Brain cells, production of steroids and cell integrity are all dependent on cholesterol.
cholesterol plays a distinct role in determining membrane fluidity. (1)
oxidized cholesterol is bad
Oxidants attack the membrane
Oxidative stress attacks the cell membranes which weaken their integrity.
Anti-oxidants protect
Anti-oxidants come in many forms, endogenous and exogenous. Endogenous means what is created within, examples of this would be glutathione, catalase and superoxide dismutase. These are created by the body with nutrient assistance. Exogenous antioxidants are taken as supplements. Well know versions are vitamins C and E but there are many others such as resveratrol, r-lipoic acid and plant based antioxidants.
Lipid peroxidation
Lipid peroxidation is the oxidation of fats, the cell membrane is subject to lipid peroxidation.
Vitamin E protects
Vitamin E protects the cell membrane.
https://www.sciencedaily.com/releases/2015/05/150519132635.htm
Leaky cell syndrome
Dr. Majid Ali is a M.E. doctor who commented on the need to infuse M.E. patients with massive doses of magnesium and potassium which are essential electrolytes. He commented that it was necessary to use high doses since the cells leaked out the nutrients due to the cell membrane damage.
Vicious cycles
Vicious cycles occur when the cell is attacked. For instance, you contract a virus, the virus stimulates the immune response, the immune response pours toxic chemicals into the bloodstream, these chemicals attack the cell membrane, the cell membrane becomes weakened, resistance is lowered, the body cannot sustain the attack.
(if the body is depleted of natural anti-oxidants such as glutathione, glutathione reduction weakens the immune response and toxins cannot be eliminated due to glutathione being depleted)
Repairing the cell may be the first step
The cell is the basis of all functions in the body and when it becomes ill then the body becomes ill.
Lactic Acid
Lactic acid (lactate) comes from cell metabolism but too much of it makes the cells weakened, likely due to impaired oxygenation and poor circulation. Too much lactic acid causes low pH (metabolic acidosis). Signs of excess lactate include generalized weakness, shallow breathing, nausea and others.
Some studies suggest that a lack of electrolytes contribute to this condition. One electrolyte, magnesium has been shown in studies to play a role. (2). Thiamine, a b vitamin was shown to be low and studies show that it along with magnesium has helped. (3)
Excess lactate can come from inflammatory conditions which include infections, toxins, trauma or depletion of body fluids (electrolytes). Check with your physician for treatment and testing.
Conclusion
The cell membrane is an integral part of health and is attacked by activation of the immune system via pathogen attack and toxins. These oxidative events attack the membrane which causes illness. Using nutrition could help repair the damage. Reduction of immune activity will stop the oxidative stress.
References
(1) The Cell: A Molecular Approach. 2nd edition.Cooper GM.
Sunderland (MA): Sinauer Associates; 2000.
(2) https://www.ncbi.nlm.nih.gov/pubmed/17063625
(3) https://www.researchgate.net/publication/304137843_TYPE_B_LACTIC_ACIDOSIS_DUE_TO_THIAMINE_AND_OR_MAGNESIUM_DEFICIENCY_IN_CRITICALLY_ILL_CHILDREN
Chapter 5
Complex Relationships
(the big picture)
In the next few chapters, I have broken down the individual component systems that play a key role in M.E. However, it should be understood that there exists a dynamic system in the body in which all systems weave into one. That when one becomes out of balance then the whole system does.
Duplicate content – but worth looking at again
Growing evidence suggests that, in addition to providing communication between immune cells, specific cytokines play a role in signaling the brain to produce neurochemical, neuroendocrine, neuroimmune, and behavioral changes. This signaling may be part of a generalized, comprehensive mechanism to mobilize resources in the face of physical and/or psychological stress and to maintain homeostasis (metabolic balance) “
Thoughts of causes of M.E.
There are a number of theories concerning the origins of M.E. which includes pathogens (viruses, bacteria, mycoplasma, yeast/fungal), genetics, toxin exposure, stress and trauma and many others. IN many cases, there is more than one problem since a single issue can crete a domino effect.
Not a closed loop system
Western medicine is beginning to understand what Eastern Medicine has understood for centuries, that the body is an interrelated and is a dynamic process, that all parts work together for the common good.
Recent studies have shown that the neurological, immune and endocrine systems all harmonize together. Stress studies show that emotional outbursts create a flood of endocrine messengers which in turn signals glands to produce strong chemicals which in turn stimulate immune responses. Immune response ends up back in the brain and now the system is awry. Muscles, joints, sleep, mood even appetite are affected as a result - the immune response becomes weakened by the onslaught of stress hormones cortisol, epinephrine and others.
Of course, the system can run the other way, immune system activation releases powerful chemicals that affect the cognitive, reasoning and emotional parts of the brain. And we all know how hormones can affect the entire body.
So, what does this all mean? The body (including the mind) is a complex system that reacts with changes.
LINK >The NEI SuperSystem is an explanation of the intricate involvement of the neurological, endocrine and immune systems. https://livingwellnessblog.wordpress.com/2015/03/15/what-is-the-nei-supersystem/
Cellular communication (cell signaling)
The body talks to itself by a complex system of hormones, neurotransmitters and a third category called paracrine/autocrine substances.
It should be noted that under most conditions that there is seldom a one cause, one solution.
Feedback system
The body is an amazing machine, more complex than science has understood. The signaling system works by monitoring the current levels of substances such as hormones and has a feedback loop system in which the hormones can be shut off or on. Think of a thermostat in your home, the thermostat acts as a monitor that controls temperature. If the thermostat senses low temperature then it signals the furnace to produce more heat, and if the temperature is low then the heat comes on.
Hormones are only part of the feedback system, the immune cells feedback and the neurological does as well, most of them interrelating to one another.
Pheromones are chemical signals that communicate not between cells but between organisms. It happens with insects, plants and humans. They are used to communicate mating signals, territories and even emotions.
Side Effects
M.E. not only deals with the complex relationships of the neurological, immune and endocrine system but other systems as well. Reduced oxidative capability disables recovery and allows the system to be in the vicious cycle. Immunity becomes decreased and confused, the liver becomes congested which limits the body’s ability to deal with harmful chemicals, muscles and joints become unreasonable, stress cycles become enhanced and volatile, sleep suffers and the cycle goes on and on.
What Works for you (The idea of bio individuality)
One of the biggest lessons I learned in this process is the role of biological individualism which means what works for others may not work for you. For instance, zinc and copper happen to be both synergistic and antagonistic, high levels of zinc will inhibit copper and vice versa and the list goes on. These relationships occur with almost every substance in our body. Every person has unique biochemical makeups from mineral balance to endocrine patterns to bowel flora, no two humans are alike.
Epigenetics is a newer field of study that shows each person has unique genetic makeup. With this unique makeup then it helps us to understand what works for one, will not work for another.
What you can do
Understand that the body is a complex organism and when it is dealing with an event then all systems will be affected. Neurological, endocrinological, immune, mood, are interlinked.
Conclusion
All systems work together to bring a single system together this is called homeostasis which is covered in the next chapter.
References
Author: R. A. Bowen http://arbl.cvmbs.colostate.edu/hbooks/pathphys/endocrine/basics/control.html
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