Myelin is the white fatty substance that wraps around the connecting branches that form between some types of brain and nerve cells. The myelin sheath can increase the speed of electrical signals between the connected cells. Disorders of myelin may be due to genetic or health conditions that occur at a young age or which increase in risk during aging. Any lifestyle or environmental situation that increases risk of excessive cell death or oxidative stress may increase risk of myelin breakdown or dysfunction in the formation of the myelinated connections between brain and nerve cells.
The medicinal value and health risks of alcohol were discussed in the last section, G11. Alcohol. Binge drinking of alcohol in excess can be a risk in the short term - an acute risk during that episode of drinking - and in the long term, excess use of alcohol can become a chronic health risk. The liver in particular is at risk to excessive alcohol use because the excess calories can not be used for energy and need to be turned into fats by the liver where it is then stored. Over time fatty liver disease can occur and may lead to damaged liver cells. The excess use of alcohol can then put the entire body more at risk due to the liver being less available to detoxify other toxins or perform other normal functions such as formation of cholesterol (G12.1, G12.2) which is part of the fatty coating that forms the myelin sheath. Chronic liver disease, including fatty liver disease, is associated with increased risk for demyelination disorders. (G12.3)
Non-alcoholic fatty liver disease may also negatively affect health similarly even though the damage to the liver had a different cause. Excessive use of fructose in the form of high fructose corn syrup sweetened products or in the form of fruit and fruit juice may be a factor in non-alcoholic fatty liver disease because fructose is not metabolized throughout the body in the same way as glucose. Fructose has to be processed by the liver similarly to alcohol and is transformed into fats which are stored in the liver when there is excessive amounts. Excessive calories in general and obesity may also be a risk factor for non-alcoholic fatty liver disease. (G12.4)
Excessive fructose intake is also a cause of increased levels of oxidative stress within the liver. Processing of fructose within the liver produces one hundred times more reactive oxidative species (ROS) than are produced during the metabolism of glucose. Antioxidant levels may then be inadequate to detoxify the reactive ROS chemicals and phosphorus from ATP may be used more quickly than in typical metabolism (ATP, adenosine tri-phosphate is the main energy unit of cellular metabolism, it provides a usable form of energy from the stored energy in carbon bonds from glucose, fructose, fats, or proteins that are metabolized/broken down for use as energy). The overproduction of ROS by mitochondria may then result in more mitochondrial dysfunction and lead to a reduction in their ability to buffer intracellular calcium levels. Protein binding with fructose also occurs more rapidly than in the presence of glucose. (G12.4) Either fructose or glucose binding with proteins can leave the protein non-functional for its normal purposes (protein fructosylation and protein glycosylation).
Summary points - excessive intake of alcohol can be a risk to the liver, (excessive alcohol use that may increase risk for liver damage has been defined as a long term intake of more than three drinks per day for men or two drinks per day for women continuing for more than five years (G12.5)); and excessive fructose intake with a normal body weight, or excessive calorie intake in general with an above average body weight (overweight or obesity) can also increase risk of liver damage. (G12.4) Liver damage increases risk for demyelination disorders due in part to increased oxidative stress and reduced cholesterol production. (G12.3)
The risk of liver damage and demyelination are also increased by smoking (G12.5) or by chronic exposure to secondhand smoke or other sources of air pollution or by significant lack of oxygen caused by other reasons due to increased oxidative stress leading to increased mitochondria and cell death. (G12.6, G12.7, G12.8, G12.9, G12.10)
Formaldehyde is a neurotoxin (G12.11) found in smoke, air pollution, and may be in some dietary sources. The topic was discussed in G3. Relaxation & Stress, and can be read as an individual topic on the blog-site effectiveselfcare.info: Formaldehyde: Health Risks, and Environmental and Dietary Sources. (G12.12)
Glutamate and aspartate are amino acids that can also act as neurotransmitters - signaling chemicals within the brain - which activate the NMDA glutamate receptors. NMDA glutamate receptors are particularly prevalent in some areas of the brain but they also may be found throughout the body. They act as gates within the membrane to either block or allow transport of ions such as calcium through the membrane ion channels. Ion channels are like tunnels through the membrane formed from a small group of specialized proteins. When excess calcium is allowed to enter the interior of the cell it may be then moved into the interior of mitochondria which can store some excess, however too much can harm the mitochondria or overload the storage capabilities of the mitochondria. Excess calcium can then cause death of mitochondria or the cell if not enough calcium can be removed or if the death of mitochondria allows too much to be released back into the cellular fluid.(G12.13, G12.14, G12.15, G12.16, G12.17)
Inflammation and glutamate excess causing oxidative stress may precede or occur at the same time as demyelination in the early stages of Multiple sclerosis. Antioxidants such as vitamin A (Retinol or beta-carotene and other carotenoids), and vitamin C (ascorbic acid) and vitamin E may help reduce oxidative stress before the oxidative stress and an increase in production of nitric oxide above beneficial levels and other reactive oxidative species can lead to demyelination.The ubiquinol form of Coenzyme Q10 (CoQ10) may also be helpful as it can regenerate the antioxidant ability of vitamin E (alpha-tocopherol is one form of vitamin E). The trace minerals zinc, copper, and manganese are also important within antioxidant enzymes. (See Table Six: G12.33, G12.34, G12.35)
Glutamate is a flavoring agent used in many processed foods that are savory in flavor such as soups and Asian foods. It may also be found along with aspartate/aspartic acid in fermented foods along with other free amino acids as the process of fermentation causes larger proteins to break down into the individual amino acids. Aspartate/aspartic acid may be found in processed foods such as baked goods or crackers as an artificial sweetener, it may not be listed on the food label in the United States however (Aspartame ™, listed on food labels, or Neotame ™, not required to be listed on the food package label). More information and a list of potential food sources is available in a pdf written for autism patient guidance. All sources can’t be avoided but if behavior or headaches or other symptoms worsen consistently after a certain food then add it to your personal avoid list. Symptom changes may occur soon after a meal that contain a lot of the flavorings or may occur the next day. The goal is to reduce total intake of glutamate or aspartate to safer levels; avoiding them one hundred percent would likely not be necessary or very possible. (G12.18)
When glucose or ketones are not available for energy use or any essential nutrients are deficient, the body will start recycling nutrients from cellular parts such as mitochondria, other organelles within the cell or from the cellular membranes (in a process called autophagy in general or mitophagy when mitochondria specifically are being recycled). If oxidative stress is occurring at rates that insufficient antioxidants are available for detoxification of the reactive oxidative species then nutrients may be also be harvested from cellular parts which may lead to mitochondria or cell death. (G12.7) When malnutrition in general, (G.41, G.42) , or specific nutrient deficiencies are occurring for longer amounts of time, then the breakdown of cellular parts may lead to a level of mitochondria death and cell death that leads to chemical signals that may cause increased amounts of demyelination of nerve cells. (G12.8, G12.9)
Nutrients used as additional supplements for patients with conditions affecting the mitochondria, the energy producing organelles found inside cells, are listed in Table 2 with dosing recommendations. From Table 2: Ubiquinol is the preferred form of CoQ10 over ubiquinone, Riboflavin, B2 and B complex are used in higher than RDA doses, L-Creatine, L-Arginine, L-Carnitine are recommended amino acids, vitamin E, C and Alpha Lipoic Acid are recommended. (G.41, Table 2) Dosing recommendations from a different source mentions that very high doses of CoQ10 may cause muscle breakdown in up to 20% of patients.
A nutrient group that is not considered essential because people of normal health and nutritional status can make the complex chemicals has been found helpful in reducing breakdown of myelin in a few ways. Cannabinoids have been found helpful in Amyotrophic lateral sclerosis (ALS),(G12.19), Multiple sclerosis, (G12.20, G12.25), Huntington’s Disease, (G12.22), and Alzheimer’s dementia in a way that might help reduce demyelination by inhibiting acetylcholinesterase enzyme. Chemical inhibitors of acetylcholinesterase have been found helpful to reduce demyelination and neuroinflammation in Myasthenia Gravis (G12.30, G12.31, G12.32) Ibuprofen has also been found to be preventative for Alzheimer’s Disease and its anti-inflammation mechanism works by reducing breakdown of cannabinoids. (page 134:G12.26, G12.27, G12.28, G12.29)
The cannabinoid group of chemicals are also available in a few food sources in the whole form or as the two main parts: phospholipids and fatty acids. More information about the chemistry and common food sources is available in the Glossary, within the Macro and Micro Nutrients section, and in an article suggesting a need for more research into supplementation with phospholipids for preventing or improving cognitive decline. (G.43)
Genetic differences, malnutrition, or changes due to aging or illness may interfere with our ability to make the chemicals internally/endogenously. The cannabinoid group help form membranes and provide flexibility to the membrane and when released from storage in the membranes can act as signaling chemicals or be transformed into other signaling chemicals. They have been found to help protect nerves from demyelination directly by activating/signaling the CB2 receptors in glial brain cells to reduce inflammation and by reducing the effects of glutamate and limiting excitotoxicity risks by activating the CB1 receptors; and indirectly by increasing antioxidant pathways which would help reduce oxidative stress.(G12.21, G12.22)
To be continuued.
“The Dartmouth Atlas Project has found that there is no correlation between higher spending and more widespread use of effective care. The causes of underuse include fragmented care (which tends to grow worse when more physicians are involved in the patient’s care) and the lack of systems to ensure that all eligible patients receive these treatments.” – (1.dartmouthatlas.org)