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Inflammation, Damage, & Repair
THE ULTIMATE ANTIOXIDANT
Inflammation plays a key role in a set of disorders that include type-2 diabetes, obesity, and heart disease—collectively called the metabolic syndrome. Epidemiologists have found that patients with type-2 diabetes and cardiovascular disease have slightly elevated levels of inflammatory markers in their bloodstream, raising the possibility that inflammation might be associated with the development of these diseases, and pro-inflammatory cytokines such as TNF-α and IL-6 promote insulin resistance in experimental models.
Inflammation itself has been well studied by immunologists: after an infection, a host of different types of immune cells are deployed to the infection site to control the infection. But the situation is different in patients with metabolic diseases: the same markers of an immune response are present, but they persist chronically at low levels instead of following the dramatic rise and fall in an infection.
Inflammation has been shown to be linked to insulin resistance and to defective insulin signaling in non-obese diabetic (NOD) mice.
Insulin resistance is the failure of the body to respond to its own insulin; it is a condition that raises blood sugar and can lead to diabetes. High doses of anti-inflammatory medications called salicylates lower the blood sugar levels of patients with diabetes.
Medicine does not recognize how subtle, constant, and easily triggered inflammatory processes can be. Eating induces an inflammatory state in everyone. Normally, inflammation occurs for three or four hours after eating, but will then taper off. Though people can’t avoid eating, they can avoid what and how much they eat. If people eat McDonald’s-type meals every three or four hours, and many do, they spend most of their time in a pro-inflammatory state.
Inflammation in blood vessels is one of the main drivers of atherosclerosis, and diabetes makes it much worse. In people without diabetes, fast blood flow triggers anti-inflammatory enzymes, endothelial nitric oxide synthase and other factors, which block the ability of pro-inflammatory immune cells to hone in on and adhere to diseased portions of blood vessels.
Pregnant women with periodontal (gum) disease have an increased risk of developing gestational diabetes mellitus than pregnant women with healthy gums. We see inflammation in diabetes with the inflammation of the gums spreading to the rest of the body through the blood vessels.
Inflammation plays a pivotal role in all stages of atherosclerosis, which is the progressive narrowing and hardening of the arteries over time.
Inflammation is the activation of the immune system in response to infection, irritation, or injury. Characterized by an influx of white blood cells, redness, heat, swelling, pain, and dysfunction of the organs involved, inflammation has different names when it appears in different parts of the body. Most allergy and asthma sufferers are familiar with rhinitis (inflammation of the nose), sinusitis (inflammation of the sinuses), and asthma (inflammation of the airways), but inflammation is also behind arthritis (inflammation of the joints), dermatitis (inflammation of the skin), and so on.
The inflammatory response can be acute or chronic. Acute inflammation typically lasts only a few days. This response usually promotes healing but, if uncontrolled, may become harmful.
Chronic, low-grade inflammation is one of the characteristics of the metabolic syndrome and interferes with insulin physiology. Ignorance has prevailed over the interrelationship between muscular lipid accumulation, chronic inflammation and insulin resistance because the central mediating factor is magnesium. It is magnesium that modulates cellular events involved in inflammation.
There are many factors that trigger inflammation. They are found in both our internal and external environments and include excessive levels of the hormone insulin (insulin resistance), emotional stress, environmental toxins (heavy metals), free-radical damage, viral, bacterial, fungal, and other pathogenic infections, obesity, over-consumption of hydrogenated oils, periodontal disease, radiation exposure, smoking, spirochetes such as the Borrelia that causes Lyme disease, and certain pharmacological drugs. Problems with insulin metabolism are a major contributor to cardiovascular disease. It results in the inability to properly store magnesium, causing blood vessels to constrict, elevated blood pressure, and coronary arterial spasm, all of which can result in a heart attack.
Excess insulin causes retention of sodium, fluid retention, elevated blood pressure, and congestive heart failure.
Inflammatory reactions in the body are a valuable predictor of impending heart attack. Persons with gingival disease (an inflammatory disorder) are 27 times more likely to suffer a heart attack than are persons with healthy gums. An American Heart Association paper disclosed that 85 percent of heart attack victims had gum disease compared to 29 percent of healthy similar patients.
When magnesium levels fall, researchers find a profound increase of inflammatory cytokines present, along with increased levels of histamine.
Magnesium deficiency causes and underpins chronic inflammatory buildups. Instead of different treatments for heart disease, Alzheimer’s and colon cancer, we apply a single, inflammation-reducing remedy that would prevent or treat these and other deadly diseases. The key words here are prevent or treat but please notice the word is not cure. Though magnesium is a cure for many of our ailments, full treatment protocols are needed. It is a protocol of basic items like magnesium, iodine, alpha lipoic acid, sodium bicarbonate, sodium thiosulfate, whole-food vitamin C, natural vitamin D from the sun, spirulina, and some other important items like purified water that will make a big difference in a host of chronic diseases.
Once we understand the critical importance of inflammation and glutathione depletion in brain diseases, we can take steps to prevent or even reverse the damage.
Inflammation and systemic stress are central attributes of many pathological conditions. In magnesium, we have found a potent medicinal that is effective across a wide-range of pathologies. Pharmaceutical companies need look no further than the seashore (except the Pacific Ocean or the Gulf of Mexico, which are highly contaminated), which contains millions of tons of magnesium chloride, the perfect anti-inflammatory agent.
There is a silent kind of inflammation that has an insidious nature and is the culprit behind diabetes and heart disease. The chronic and continuous low-level stress that silent inflammation places on the body’s defense systems often result in an immune system breakdown. Magnesium deficiency is a parallel silent insult happening at the core of our physiology. Magnesium deficiencies feed the fires of inflammation and pain. We could very well be suffering from magnesium deficiency, but we most likely will not know it until we suddenly have a cardiac arrest.
Epidemiologic studies have shown an inverse relationship between magnesium in the drinking water and cardiovascular mortality. This association between magnesium in drinking water and ischemic heart disease was reconfirmed in a major review of the literature done by epidemiologists at Johns Hopkins University. Since most heart disease is marked by various levels of inflammation, these studies are all highlighting the hidden relationship between inflammation and magnesium deficiency.
Beyond all the common symptoms of inflammation, the body tissues themselves may lose their ability to recognize the difference between cells that are “self” and those that are not, and the body may thus mistakenly identify its own cells as foreign invaders. This internal programming error then continues to trigger and retrigger immune responses, setting the stage for autoimmune diseases such as lupus, multiple sclerosis, and scleroderma. The result is cellular chaos, and this process may be happening year after year without our even being aware of it.
This chronic inflammatory response breaks down healthy tissue in a misdirected attempt at repair and healing.
Doctors who specialize in rheumatoid arthritis, multiple sclerosis, lupus, and other autoimmune disorders are very familiar with what happens when the body goes to war with itself. These diseases demonstrate a direct inflammatory attack against healthy cells in places such as the joints, nerves, and connective tissue.
Atherosclerosis is caused by chronic inflammation, which often begins very early in life. The big dispute among experts is what causes the inflammation in the first place. One theory holds that bacteria and viruses may cause this inflammation, but clearly we know that lead, mercury, monosodium glutamate (MSG), fluoride, and other toxic chemicals can also cause inflammatory reactions in blood vessels.
Recent advances in the field of cardiovascular medicine have emphasized the involvement of inflammation in the formation of atherosclerotic plaque.
Magnesium is at the heart of the inflammatory process; it is the prime first cause when it is not present in sufficient quantities. Increases in extracellular magnesium concentration cause a decrease in the inflammatory response while reduction in the extracellular magnesium result in inflammation. Inflammation causes endothelial dysfunction and activated endothelium facilitates adhesion and migration of cancer cells.
Chronically inflamed tissues continue to generate signals that attract leukocytes from the bloodstream. When leukocytes migrate from the bloodstream into the tissue, they amplify the inflammatory response.
Magnesium literally puts the chill on inflammation, especially when used transdermally. Heart disease begins with inflammatory chemicals that rage like a fever through your blood vessels. You can cool the heat by getting the recommended daily minimum of magnesium. Those who get less than 50 percent of the RDA (310-420 mg) for magnesium were almost three times as likely to have dangerously high C-reactive protein (CRP) levels as those who consumed enough. Being over age 40, overweight, and consuming less than 50 percent of the RDA more than doubles the risk of blood-vessel-damaging inflammation.
Women who get more magnesium in their diet are less likely to have the metabolic syndrome, inflammation in the body, and heart and blood vessel disease. Women who have the highest magnesium intake have 12 percent lower C-reactive protein levels than women with the lowest magnesium intake. The magnesium found in a healthy, well-balanced diet can protect the body against inflammation and high blood glucose, conditions that can lead to type-2 diabetes and heart and blood vessel disease.
Chronic inflammation destabilizes cholesterol deposits in the coronary arteries, leading to heart attacks and strokes.
Most coronary heart disease starts as an endothelial infection and, in most cases, is caused by pathogens. Recognizing the role of inflammation in arteriosclerosis represents a huge paradigm shift for cardiologists. The American College of Cardiology, the American College of Physicians, and the American Heart Association largely ignore the involvement of inflammation in heart attacks and strokes and certainly they ignore unresolved psycho-emotional trauma, as well as the toxic buildup of mercury, which can lead to massive heart failure and sudden death even in the healthiest athlete.
Inflammation not only further damages the artery walls, leaving them stiffer and more prone to plaque buildup, but it also makes any plaque that’s already there more fragile and more likely to burst.
As consumption of magnesium falls, the level of C-reactive protein goes up. C-reactive protein (CRP) is produced in the liver and is a strong predictor of cardiovascular events, such as heart attacks and stroke, even where cholesterol levels may be normal. CRP levels in the blood are normally undetectable or very low; high levels are strongly associated with inflammation. High CRP levels indicate a greater risk of diabetes.
Inflammation is the missing link to explain the role of magnesium in many pathological conditions.
This new view of inflammation is changing the way some doctors practice, but most cardiologists are still not ready to recommend that the general population be screened for inflammation levels. There continues to be a blind spot in cardiologists’ perceptions. They just are not able to get to the bottom of the inflammation story—magnesium deficiency.
Magnesium decreases swelling and is effective in the treatment of inflammatory skin diseases.
Whatever makes us become less efficient at using insulin is going to aid in the development of diabetes. Treatments for diabetes work by replacing insulin, boosting its production, or helping the body make more efficient use of the hormone.
The use of magnesium as an anti-inflammatory makes magnesium absolutely indispensable to not only heart patients, but also to diabetics, neurological and cancer patients as well. The treatment of chronic inflammation has been problematic for medical science because most of their pharmaceuticals create more inflammation by further driving down magnesium levels.
Virtually all the components of the metabolic syndrome of diabetes, high blood pressure, obesity, and lipid disorders are associated with low magnesium. The entire metabolic syndrome is nothing but a manifestation of a magnesium deficiency. There is no single food that contains huge amounts of magnesium, and there is no magnesium lobby. Thanks to the dairy industry, we are constantly told that we need to get enough calcium, and we’re told right where we can get it. Milk and cheese. Same with Vitamin-C. Not so with magnesium, so no one really thinks of it. Another reason that many people are magnesium deficient is that they drink bottled water or softened water. In the old days, everyone drank well water or water from streams, both of which contain large amounts of magnesium. Magnesium is removed when water is softened, and it isn’t in large amounts in most of the bottled waters that are available.
Inflammation contributes to the pro-atherogenic changes in lipoprotein metabolism, endothelial dysfunction, thrombosis, and hypertension; this explains the aggravating effect of magnesium deficiency on the development of metabolic syndrome.
Magnesium deficiency induces a systemic stress response by activation of neuro-endocrinological pathways. Magnesium deficiency contributes to an exaggerated response to immune stress, and oxidative stress is the consequence of the inflammatory response. Long-term air pollution exposure is associated with neuro-inflammation, an altered innate immune response, disruption of the blood-brain barrier, untrafine particulate deposition, and accumulation of beta amyloid -42 and alpha-synuclein in children and young adults.
The lipid hypothesis of heart disease causation is rapidly being supplanted by the inflammatory hypothesis. Elevated cholesterol in combination with an elevated c-reactive protein is a better gauge of heart disease risk. It seems that without the inflammation, elevated cholesterol is not a threat after all.
Inflammation is a response from our immune systems to irritants. If you sprain your ankle, your immune system creates a protein called a circulating immune complex (CIC). The CIC travels down to the injured ankle and causes pain and swelling. The pain you feel is for the purpose of informing you of the injury or damage. And the swelling is protective as it prevents you from moving it and causing more irritation. This is also the body’s way of running to the problem with fresh blood, antibodies, and vital cells in order to begin healing and repairing the damage.
The body then produces proteolytic enzymes that counteract the inflammation, and things return to normal. That’s why a sprained ankle in a young child heals within a few weeks at most, but in a middle-aged adult, can take six weeks or more. After around age 25, our production of these enzymes drops off almost completely, so there is nothing to tell the body to stop the inflammation. These enzymes are also responsible for cleaning the blood, fighting off viral and bacterial infections, and breaking down excess fibrin (scar tissue). Most, if not all, of these enzymes are mediated by magnesium, meaning as magnesium levels drop off, so do the activities of these crucial biological magnesium-sensitive enzymes.
Enzymes break down scar tissue and fibrosis. Fibrosis is scar tissue that builds up in our bodies and over time, creates so much restriction and strain on our organs that they can no longer function properly. Enzymes also clean the blood of excess fibrin that causes the blood to thicken, which sets us up for clots, which can cause heart attacks or strokes. Enzymes also help take some of the strain off of the liver by keeping the blood clean and not allowing it to thicken beyond normal. Enzymes are very important in inflammation; the fundamental supporter of enzymes is magnesium.
Pain management with magnesium employs magnesium chloride applied to the skin (transdermally). Magnesium chloride, when applied directly to the skin, is transdermally absorbed and has an almost immediate effect on chronic and acute pain. Most pain and anti-inflammatory medications are not safe; even the over-the-counter pain medications hold unforeseen dangers. More than a decade’s worth of research shows that taking too much acetaminophen can ruin the liver; the number of severe, unintentional poisonings from the drug is on the rise. Acetaminophen is known under the brand name Tylenol. Compounds containing Tylenol include Excedrin, Midol Teen Formula, Theraflu, Alka-Seltzer Plus cold Medicine, and NyQuil Cold and Flu, as well as other over-the-counter drugs and many prescription narcotics like Vicodin and Percocet.
While many species of bacteria activate inflammation, it is when bacteria initiate chronic inflammation that cancer risk increases significantly. Changes in human diet affect our microbiota, and the answers are teasingly complex. We can’t think of the food we ingest without thinking of the gut bacteria that also ingest our food. One oft-cited example is the polyphenol family of chemicals, predominantly found in coffee, tea, wine, fruits, and vegetables, which have been linked to reducing the risk of cancer…Polyphenols are not digested and absorbed in the upper gastrointestinal tract, but they are readily metabolized in the colon by microbial enzymes.
A healthy redox balance depends on a fluid shift between glutathione synthesis and methylation, especially when responding to environmental toxins, stressors, or infections. Two B vitamins, folate and cobalamin (B12), are absolutely essential for this fluid, dynamic shift. Most important, the body must be able to adequately convert both nutrients to their active forms, so they can do their job in helping the body methylate when needed, and make more glutathione when needed.
Methyfolate is the only substance that can donate a methyl group to B12, making the all-important and highly active methylcobalamin.
Folate occurs naturally in many foods. Foods high in folate include leafy green vegetables (such as spinach, chard, turnip greens, romaine, broccoli), citrus fruits and papaya, cantaloupe, pineapple, honeydew and bananas, eggs, beans, peas, as well as beef liver. Different forms of folate—before its conversion to methylfolate—play many important roles in the body. They help regulate the healthy growth of new cells, which is especially important for an embryo and newborn. They are necessary to make both DNA and RNA, and help protect DNA from mutations that might lead to cancer.
They are crucial to making normal red blood cells (they help form heme, the iron-containing protein in hemoglobin), and it is essential for metabolizing homocysteine so that this amino acid doesn’t build up to unhealthy levels. Because folate is so important, the Food and Drug Administration published regulations in 1996 requiring that the synthetic form of folate, called folic acid, be added to breads, cereals, flours, pastas, rice and other grain products so commonly eaten by Americans. This helped prevent birth defects and miscarriage, since folate is needed during pregnancy and early life. Thus today, grains are also a source of the synthetic form of folate, folic acid.
Though folic acid is stable and has a long shelf life, the body must convert it into folate in order to use it. Studies show transformation of folic acid falls off after ingesting 200 mcg, and is saturated around 400 mcg. When it is not converted, it can remain in the bloodstream for days, even weeks at a time. In addition, there is some conflicting evidence that high-dose supplementation of folic acid may contribute to risk of certain cancers.
On the other hand, dietary folate seemed protective, although not at a rate that was statistically significant. The researchers conclude: “These findings highlight the potential complex role of folate in prostate cancer and the possibly different effects of folic acid-containing supplements vs. natural sources of folate.” However, one issue they sidestep is whether a synthetic supplement, folic acid, that has to be converted back to folate, may itself cause problems.
Genetic variations mean that some of us have trouble converting B12 to the active forms.
Although the body has many uses for folate, one is to serve as a building block for methylfolate. Methylfolate is the only substance than can donate a methyl group to B12, making the all-important and highly active methylcobalamin. Because of genetic variation, some people are less efficient at conversion, and when their bodies are stressed they may not make enough methylfolate. Then their ability to methylate and to make glutathione will be impaired, contributing to many chronic health problems. Testing can help determine if conversion capacity is low. Supplements of methylfolate are available, in a calcium salt form of 5-methyltetrahydrofolate, and in a newly available form, a glucosamine salt of 5-methyltetrahydrofolate, which has demonstrated greater solubility and bioavailability in preliminary studies. The new 5-MTHF glucosamine salt was shown to be approximately 100 times more soluble and increased plasma levels 20% higher in rats and 10% higher in humans than the calcium salt form.
Cobalamin, or B12, is a very interesting vitamin, which actually contains the mineral cobalt, giving it that lovely, striking red color. In 1934, three researchers won the Nobel Prize for the discovery that eating large amounts of raw liver, which contains high amounts of vitamin B12, could save the life of incurable patients with fatal pernicious anemia. This finding saves 10,000 lives in America each year. The vitamin itself was isolated from liver extract in 1948 and its structure was characterized 7 years later.
Deficiency of vitamin B12 impairs DNA synthesis, affecting the growth and repair of all cells. Everything from anemia to neuropathy, weakness, loss of appetite or taste and smell, irritability, memory impairment, tingling and numbness can be symptoms of Vitamin B12 deficiency.
B12 can be converted by the body to an active form known as adenosylcobalamin. This form interacts with the enzyme methylmalonyl CoA mutase and is used by the mitochondria, the energy powerhouse of the cell. Vitamin B12 can also be converted to another active form, methylcobalamin. Methycobalamin is a cofactor for the enzyme methionine synthase, and is a key nutrient in both methylation and in regulating the synthesis of glutathione. As with folic acid, supplements of B12 are often available in a synthetic form called cyanocobalamin, which has a long shelf life, but must be converted by the body back into a useable form. In addition, the body’s ability to absorb B12 from typical oral dietary supplements is limited by the capacity of something called intrinsic factor, a glycoprotein secreted by the stomach. Only about 10 mcg of a 500 mcg oral supplement is absorbed by healthy people, simply because it exceeds the ability of available intrinsic factor.
We cannot make our own B12. Bacteria in our gut can make it for us and other mammals. Naturally occurring B12 is found in animal products, including fish, meat, poultry, eggs, milk, and milk products. Vitamin B12 is generally not present in plant foods, but like folic acid, certain foods such as breakfast cereals are fortified with it in a cyanocobalamin form. As we age, we can have more difficulty absorbing B12 from food. In fact, many of us may be deficient in B12.
Genetic variations mean that some of us have trouble converting B12 to the active forms. Urine tests can reveal deficiencies of the active forms even when blood tests show adequate B12.
Surprising new research demonstrates that diabetic neuropathy, an extremely painful condition, may respond to supplementation with the active forms of three b vitamins: methyl B12, methylfolate, and the active form of vitamin B6 (pyridoxal-5'-phosphate). Major depression responded to methyfolate in combination with antidepressants in a 2011 study.
Methylfolate alone may sometimes be useful in clinical depression. A 2009 report and review from Harvard Medical school notes that folate is needed for the synthesis of norepinephrine, serotonin and dopamine.
Another 2011 study finds that methyl B12 rescues neurons from homocysteine-mediated cell death. Excess homocysteine is known to be toxic to neurons and can initiate cell death. Methyl B12 was able to reduce levels of an enzyme, caspase, involved in cell death. The researchers concluded that methyl B12 might be useful in treatment of late stage ALS, since homocysteine levels have been found to be increased in animal models of the disease.
Autism also responds to treatment with methycobalamin. The researchers report that there were “significant increases in cysteine, cysteinylglycine and glutathione … the oxidized disulfide form of glutathione was decreased...targeted nutritional intervention with methylcobalamin and folinic acid may be of clinical benefit in some children who have autism.”
In the simplest terms, maintaining life can be viewed as the ability to resist oxidation. Oxygen is essential to life, but oxygen is like fire. It can be very damaging and needs to be controlled by antioxidants, known as “reducing” molecules. Balancing reduction and oxidation—or redox—is the fundamental challenge of life. What’s great about that word, redox, is that it shows that they are profoundly linked and we need both. Once you understand this relationship, it leads to all kinds of new insights.
From the very moment of conception, life can be sparked by the unique redox environment created when a sperm fertilizes an egg. The sperm is extremely rich in proteins containing the mineral selenium, which is a potent reducing agent for glutathione, the most important antioxidant molecule in cells. The egg, on the other hand, is very rich in glutathione. Bring these two potent antioxidant strategies together, and you create an exceptionally reduced cell that can initiate life and promote development using the power of redox. That reducing power provides a metabolic spark as new life begins its journey, allowing the rapidly dividing cells to safely maintain a high rate of oxidation. The same metabolic challenge continues as the embryo develops. The entire nervous system and the shaping of gene activity are profoundly influenced by this redox balance as well. Aging is essentially a process of gradual oxidation, and our health as we age depends on successfully quenching that oxidation. Finally, innumerable diseases are linked to high levels of oxidation and low levels of glutathione—from schizophrenia to major depression, autism, chronic fatigue syndrome, fibromyalgia, and most chronic autoimmune and chronic inflammatory diseases.
Glutathione is made from cysteine, glycine, and glutamic acid. You can get cysteine from the diet, in meat, eggs, garlic, onions, red pepper, broccoli and other foods. Cells in the gut lining, aided by transporter molecules, will bring it into the body. Both gluten (found in grains such as wheat) and casein (milk protein) can inhibit the uptake of cysteine, which the body needs to make glutathione. So many children with autism, or adults with autoimmune disorders, do better when they eliminate wheat and milk from their diet. It’s due to a redox mechanism.
Both casein and gluten are broken down into certain peptides that are relatively stable. The protein casein is broken into casomorphins. The “morphins” are so named because, like morphine, they act on the opiate receptors. The most famous one, beta casomorphin 7 (BCM7), has seven amino acids. Our recent research shows that BCM7 first stimulates the uptake of cysteine, but then inhibits it. However, the human BCM7 is markedly different than bovine BCM7 from the cow. It turns out that the BCM7 from a cow inhibits cysteine at least twice as much as the BCM7 from a human mother. The implications for health are profound if you start thinking about formula feeding and all the dairy products from cows in our diet. Breastfeeding is clearly regulating the redox system of newborns. A diet high in dairy from cows can promote a decrease in our antioxidant capacity, our ability to make enough glutathione.
The peptide from sheep’s milk behaves more like human milk. Similarly, the protein in gluten is known as gliadin, and it also creates a seven amino acid peptide, like BCM7. We already know that gliadin can trigger celiac disease, and can also lead to gluten intolerance and sensitivity. These problems reflect the ability of gluten peptides to inhibit cysteine uptake, perhaps contributing to chronic inflammation, although we have more to learn about that. Of course, not everybody who eats diary or wheat has poor antioxidant capacity, and milk and wheat are important sources of nutrition. There are probably genetic vulnerabilities that bring some people closer to a critical point for oxidative stress, while for others it is a non-issue. Overall, though, this is an issue to consider in any chronic inflammatory disease or neuro-immune disease.
Methylation and glutathione are very tightly intertwined. There is a critical metabolic intersection—a fork in the road—where cells must decide to either make more glutathione, or support more methylation. The overall balance between these two options is crucial to health.
Your body can take homocysteine and convert it back to cysteine. Homocysteine is a metabolite of the essential amino acid methionine, and elevated levels have been associated with vascular disease. Homocysteine is created when methionine donates its methyl group to another molecule in a process known as methylation.
Methylation is a fundamental process of life which is intimately linked to redox status. In chemistry, a methyl group is a hydrocarbon molecule, or CH3. When a substance is methylated, it means that a CH3 molecule has been added to it. Methylation can regulate gene expression, protein function, even RNA metabolism. It can suppress viruses, even latent viruses or cancer viruses we are born with and can help us handle heavy metals. In the liver in particular, methylating a toxin helps change it to a form of the compound that can be more easily processed and excreted.
Methylation is an extremely broad and fundamental action that nature uses to regulate all kinds of processes. It regulates epigenetic changes—changes to gene expression that occur because of environmental factors—by affecting how DNA unravels during development. Some changes can be permanent for the whole lifespan and can even be passed down as many as three generations. That shows that the environment, through the process of methylation, can be quite a profound influence. There are 150-200 methyl transferase enzymes, and each enzyme can methylate multiple targets. So you can imagine methylation as a spider’s web within each cell, and that web branches out in many directions.
Methylation and glutathione are very tightly intertwined. There is a critical metabolic intersection—a fork in the road—where cells must decide to either make more glutathione, or support more methylation. The overall balance between these two options is crucial to health, and this occurs with homocysteine. When methionine gives away its methyl group, we’re left with homocysteine. And the body has to decide, should homocysteine be methylated, and go back into methionine, or should it be converted into cysteine, so that the body can make more of the antioxidant glutathione? This fundamental decision is made again and again by the body, and the overall balance is crucial to health. Too little glutathione and we will end up with free radical, oxidative damage. Not enough methylation, and many genes and viruses will not be properly regulated. Excess homocysteine, and the risk of vascular disease goes up.
It’s important to understand that multiple factors impinge on the same system. What’s so important here is that the glutathione antioxidant system is a common target for so many different environmental toxins and infections. Every single one of them impinges on the glutathione system. It’s not that each molecule of mercury or lead picks off one glutathione molecule. No. It’s that in general, environmental assaults inhibit the enzymes that are responsible for keeping the glutathione in its reduced antioxidant state, where it can do its job. The potent ability of mercury to inhibit selenium-containing enzymes is a good example.
Some people sail through these stressors and remain healthy, while others stumble and fall. Though many molecules and nutrients are important, the active forms of vitamin B12 (adenosylB12 and methylB12) and the active form of folate (methylfolate) are essential to this process. Once you have the raw material to make glutathione or to methylate, you need cofactors like methylfolate and methyl B12 to complete the process. If we don’t make enough of these active forms, we will not be able to smoothly and fluidly shift between methylation and glutathione.
Nature allows, and even encourages, genetic variation, and the bottom line is that some people have genetic variations that render this process less functional. Even with a less functional genetic legacy, you might be fine if you are not stressed by the environment—in particular by chronic infections or toxic assaults. Stress brings out limitations in genes that otherwise are latent and not problematic. That’s a general truth. So yes, with proper testing by a doctor to see if there is a functional deficiency, supplementation with active forms can help. For example, there is a test that measures levels of methylmalonic acid (MMA) in the urine; if the levels are high, you are not making enough of the two active forms of B12. Your serum B12 may be perfectly normal—you just aren’t converting enough of it to the active form.
We ourselves cannot make B12, also known as cobalamin. Bacteria make it for us, and since vegetables don’t carry those bacteria, vegans can be deficient in B12. B12 is such a precious material for the body that if, for instance, you eat a piece of rib eye steak, the B12 released from the proteins is instantly bound right there in the GI tract and chaperoned as if in a football handoff to be carried to cells, transported inside and then processed into the two active forms. Nature knows this is a precious material for life, and a critical indicator of cellular oxidation status.
There are several natural forms of B12 which need to be converted into the active forms, adenosylB12 and methylB12. CyanoB12, the form in most vitamin supplements, is not active and is less useful than the active forms for treating deficiency states. Glutathione itself is needed for converting other forms of B12 to the active forms. Indeed, there is a type of cobalamin called glutathionylcobalamin that is an intermediate for making the active forms.
There are two enzymes in the human body that require active B12 as a cofactor. One is called methylmalonyl CoA mutase, and it needs adenosylB12. It is an enzyme that is necessary for the mitochondria—the energy powerhouse of your cell—to function. The other enzyme that requires active B12 is the enzyme methionine synthase, which requires methyl B12.
MethylB12 is constantly recycled. It donates its methyl group to homocysteine, which then turns into methionine. Once B12 is missing its methyl group, it needs to get a fresh one. And that’s where methylfolate comes in. Methylfolate is in essence a methyl donor for methionine synthase. That’s its job in life. It is the only molecule than can donate a methyl group to B12. Once it does that, the rest of the folate is available to go out and support all kinds of other reactions in the body that need plain folate.
When your level of methylB12 is low, homocysteine builds up and this can have adverse health effects. High homocysteine levels in the blood reflect low activity of the enzyme methionine synthase, and this has been linked to an increased risk of atherosclerosis and coronary artery disease. It is also well known that homocysteine levels are increased in Alzheimer’s disease, which suggests a role for impaired methylation in this neurodegenerative disorder. Of course low B12 levels are classically associated with pernicious anemia and with peripheral neuropathy.
Low levels of folate are also classically associated with anemia, heart disease, fetal abnormalities such as spina bifida, as well as neuropathies and these have been specifically linked to a deficiency in methylfolate. In addition, recognition of the important role of methylfolate and vitamin B12 in supporting D4 dopamine receptor methylation links their deficiency to impaired attention such as attention-deficit hyperactivity disorder (ADHD). People with genetic polymorphisms in the enzyme that makes methylfolate are particularly vulnerable to a deficiency.
Some research has shown that synthetic folic acid can build up when supplemented, and a few studies have suggested this may even be linked to cancer in high doses.
In addition to vitamin B12 and methylfolate, there are several other nutritional supplements whose actions are critical for redox and methylation pathways. Vitamin B6 (pyridoxal-5-phosphate or P5P) is an essential cofactor for the two enzymes that sequentially convert homocysteine to cysteine, namely cystathionine-beta-synthase and cystathionine-gamma-lyase. Together these two B6-dependent enzymes comprise the transsulfuration pathway that promotes glutathione synthesis. The common supplement form of vitamin B6, pyridoxine, must be converted to the active form, and in some disorders, such as autism, this conversion is impaired, so the P5P form may be more effective. N-acetylcysteine (NAC) provides a supplementary source of cysteine. NAC can cross into the cell cytoplasm where the cysteine is released and allowed to promote glutathione synthesis. SAMe is an active, methyl-donating derivative of the essential amino acid methionine, and during oxidative conditions its levels may be low, due to low methionine synthase activity. SAMe has shown particular benefit in treating depression.
These examples of the interrelationship between oxidation and methylation are just the tip of the redox iceberg. Nature has learned to harness the power of oxidation as a signaling mechanism to control cellular activity. When more antioxidant is made available, cells can safely undertake a higher level of metabolic activity. There is a lot more to learn, and the real challenge will be to convert this evolving knowledge about redox and methylation into new, more effective treatment strategies.
FMS (fibromyalgia syndrome) is a widespread musculoskeletal pain and fatigue disorder for which the medical profession says the cause is still unknown. Fibromyalgia means pain in the muscles, ligaments, and tendonsthe soft fibrous tissues in the body. Most patients with FMS say that they ache all over. Their muscles may feel like they have been pulled or overworked. Sometimes the muscles twitch and at other times they burn. More women than men are afflicted with FMS, and it shows up in people of all ages.
Long term studies on FMS have shown that it is chronic, but the symptoms may wax and wane. The impact that FMS can have on daily living activities, including the ability to work a full-time job, differs among patients. Overall, studies have shown that FMS can be equally as disabling as rheumatoid arthritis. It is the latest “designer disease," and is a catchall, "wastebasket" diagnosis.
FMS is not a “disease,” as a disease has to be communicable and have an incubation period, which neither are found in FMS. FMS is called a “syndrome,” which means it is a specific set of signs and symptoms that occur together. Rheumatoid arthritis, lupus, and other serious afflictions are also classified as "syndromes." There is no blood test that can accurately identify fibromyalgia.
Most patients, when questioned carefully, reveal that their symptoms began at an early age. Flu-like achiness is frequently the most prominent symptom of FMS, but there are many others. The official definition for patients to be admitted into a clinical study requires that tender points must be present in all four quadrants of the body that is, the upper right and left and lower right and left parts of your body. You must have had widespread, more-or-less continuous pain for at least three months.
FMS is a sensitivity-amplification syndrome. This means that people diagnosed with fibromyalgia can be sensitive to smells, sounds, lights, odors, pressure and temperature fluctuations and vibrations. The noise emitted by fluorescent lights can drive them crazy. FMS sufferers have sensitized nerve endings as well as the rest of the autonomic nervous system, which means that the ends of the nerve receptors may have changed shape or are hyper-irritable. Because of this, their body might interpret touch, light, or sound as pain. Your brain knows pain is a danger signalan indication that something is wrong and needs attentionso it mobilizes its defenses. Then, when those defenses aren't used, they become anxious.
It was first described by William Balfour, a surgeon at the
The Medical profession says the cause of FMS remains elusive, but believes there are many triggering events thought to precipitate its onset. A few examples would be an infection (viral or bacterial), an automobile accident or the development of another disorder, such as rheumatoid arthritis, lupus, or hypothyroidism.
Pain The pain of FMS has no boundaries. People describe the pain as deep muscular aching, throbbing, shooting, and stabbing. Intense burning may also be present. Quite often, the pain and stiffness are worse in the morning and you may hurt more in muscle groups that are used repetitively. Myofascial pain is probably the most common cause of musculoskeletal pain in medical practice. A small change in the myofascia can cause great stress to other parts of your body.
Fatigue This symptom can be mild in some patients and yet incapacitating in others. The fatigue has been described as "brain fatigue" in which patients feel totally drained of energy. Many patients depict this situation by saying that they feel as though their arms and legs are tied to concrete blocks, and they have difficulty concentrating, e.g., brain fog.
Sleep disorder Most FMS patients have an associated sleep disorder called the alpha-EEG anomaly. Researchers found that most FMS patients could fall asleep without much trouble, but their deep level (or stage 4) sleep was constantly interrupted by bursts of awake-like brain activity. Patients appeared to spend the night with one foot in sleep and the other one out of it. Sleep lab tests may not be necessary to determine if you have disturbed sleep. If you wake up feeling as though you've just been run over by a Mack truckwhat doctors refer to as unrefreshing sleepit is reasonable for your physician to assume that you have a sleep disorder. Many FMS patients have been found to have other sleep disorders in addition to the alpha-EEG, such as sleep apnea, sleep myoclonus (nighttime jerking of the arms and legs), and restless legs syndrome.
Irritable Bowel Syndrome Constipation, diarrhea, frequent abdominal pain, abdominal gas, and nausea represent symptoms frequently found in roughly 40 to 70% of FMS patients.
Chronic headaches Recurrent migraine or tension-type headaches are seen in about 50% of FMS patients and can pose a major problem in coping for this patient group.
Temporomandibular Joint Dysfunction Syndrome This syndrome, sometimes referred to as TMJ or TMD, causes tremendous jaw-related face and head pain in one quarter of FMS patients. However, a 1997 published report indicated that close to 75% of FMS patients have a varying degree of jaw discomfort. Typically, the problems are related to the muscles and ligaments surrounding the jaw joint and not necessarily the joint itself.
Other common symptoms Premenstrual syndrome and painful periods, chest pain, morning stiffness, cognitive or memory impairment, numbness and tingling sensations, muscle twitching, irritable bladder, the feeling of swollen extremities, skin sensitivities, dry eyes and mouth, dizziness, and impaired coordination can occur. Patients are often sensitive to odors, loud noises, bright lights, and sometimes even the medications that they are prescribed.
Aggravating factors Changes in weather, cold or drafty environments, hormonal fluctuations (premenstrual and menopausal states), stress, depression, anxiety and over-exertion can all contribute to symptom flare-ups.
Fascia is all continuous and three dimensional. Superficial fascia is attached to the underside of your skin. Capillary channels and lymph vessels run through this layer, and so do many nerves. The subcutaneous fat is attached to it. If your superficial fascia is healthy, your skin can move fluidly over the surface of your muscles. In FMS and CMP, it is often stuck. In the superficial fascia, there is a great potential to store excess fluid and metabolites, which are the breakdown products of informational substances and other chemicals in your body. This is the area of fascia that often is the easiest to palpate. Palpation is the art and skill of being able to touch meaningfully, interpreting what the skin and fascia are willing to tell about your state of health.
Deep fascia is much tougher and denser material. Your body uses deep fascia to separate large sections, such as the abdominal cavity. Deep fascia covers some areas like huge sheets, protecting them and giving them shape. Deep fascia also separates your muscles and organs. The bag-like covering around your heart (the pericardium), the lining of your chest cavity the pleura), and the area between your external genital and your anus (the perineum) are all made up of specialized deep fascia.
There is a third layer of fascia, called sub serous fascia. This is loose tissue that covers your internal organs and holds the rich network of blood and lymph vessels that keep them moist. Even your cells have a type of cytoskeleton connected to fascia network, which is what gives your cells shape and allows them to function. Myofascia is fascia that is related to muscle tissue. Healthy myofascia allows for compression and tension, as well as relaxation.
The dural tube is another fascial connection. This is the tube surrounding and protects your spinal cord, and it contains the cerebrospinal fluid. This tube is connected to the membranes surrounding your brain. Together, they hold and protect your craniosacral system.
Fascia is also the material that forms adhesions and scar tissue. When you are healthy, your ground substance has a gelatinous consistency so that it can absorb the forces that are created when you move, or if you are involved in trauma. When the ground substance hardens, it’s as if glue or cement has been poured into our fascial spaces. When this happens, it isn’t enough for a therapist to break up cross-links. They need to return your ground substance to its healthy, more fluid state.
In the myofascia there is a material called ground substance. The ground substance part of the fascia can be like a loose gelatin, or like gel-foam medical packing, or like sprayed on Styrofoam insulation. It can harden and lose its elasticity. When ground substance changes from a liquid to a gel, and then into its more solid form, the myofascia tightens. It won’t reverse to its previous more liquid state without outside intervention. One of the main jobs of the ground substance is transferring nutrients from where they are broken down into usable materials to their place where they will be used, and to remove the waste products from these areas of use. This exchange and transport through diffusion takes part in the ground substance.
Another important job for your ground substance is to maintain the distance between connective tissue fibers. This prevents microadhesions from forming, and keeps your tissues supple and elastic. When the critical distance is not maintained, the fibers become cross-linked by newly synthesized collagen, which are also part of the fascia. Collagen cross-links are arranged haphazardly, unlike healthy linkages, and are hard to break up.
Sheets of fibrous myofascial adhesion can form anywhere along nerves and block normal healthy function. Too often, fascia has been considered by the medical world as merely packing material, simply a connective tissue between areas of function. The mobility, elasticity, and slipperiness of living fascia can never be appreciated by dissecting embalmed cadavers in medical school.
Where muscles and tendons, bones and ligaments come together, there are areas of attachment. The cellular membranes in these attachment areas can become extremely convoluted, which increases the surface area and changes the angle of force. This increases the potential for things to get stuck together, and causes the tissue there to become more easily torn.
Trigger Points (TrPs) are found as extremely sore points occurring in ropy bands throughout the body. They can also be felt as painful lumps of hardened fascia. The bands are often easier to feel along the arms and legs. If you stretch your muscle about 2/3 of the way out, you might be able to feel them. Sometimes the muscles get so tight that you can't feel the lumps, or even the tight bands. Your muscle feels like "hardened concrete". TrPs can occur in the myofascia, skin, ligaments, bone lining, and other tissues. They can be caused by a surgical incision, as is often the case with abdominal surgery. You have probably never heard of TrPs, yet they are quite common. Each specific TrP on the body has a referred pain or other symptom pattern that is carefully documented.
When muscles are in a state of sustained tension, they are working, even if you're not. A working muscle needs more nutrition and oxygen, and produces more waste, than a muscle at rest. This creates an area in the myofascia starved for food and oxygen, and loaded with toxic wastea trigger point. Dizziness, ringing of the ears, loss of balance, and other symptoms can all be caused by TrPs in the side of the neck, in the muscle group called the sternocleidomastoid (SCM) complex. This muscle has many functions, one of which is to hold your head up. Receptors in the SCM complex transmit nerve impulses inform the brain of the position of the head and body in the surrounding space. With TrPs, the receptors lie. What they tell the brain is not what the eyes tell the brain. If there are TrPs in the muscles of the the eyes, they are lying tooonly probably not in the same way as the SCM. A common symptom of SCM TrPs is a "drunken" walk, as we bump into doorways and walls. An active TrP not only hurts when it is pressed, like an FMS tender point, but it "triggers" a referred pain pattern somewhere else in the body. This pain pattern is similar from patient to patient. These trigger points often produce other symptoms, also usually in the referred pain zone. Such a TrP hurts whenever you use the involved muscle. When the point becomes very active, pain and other symptoms occur even when the muscle is at rest.
If TrPs are treated immediately and vigorously, and perpetuating factors (conditions that aggravate and perpetuate the TrPs, are avoided or remedied, TrPs can be eliminated. Unfortunately, if TrPs are left untreated, are inappropriately treated, or muscle action is restricted to avoid pain, the TrP usually becomes latent. If the muscle is pushed to work in spite of the pain, especially if perpetuating factors exist, active TrPs may develop secondary and satellite TrPs.
A "latent" type of TrP also occurs. The latent TrP doesn't hurt at all, unless you press it. You might not even know it's there, but your body does. It restricts movement, weakens, and prevents full lengthening of the affected muscle. If you press on the TrP, it refers pain in its characteristic pattern. Latent TrPs may be activated by overstretching, overuse, or chilling the muscle. People who get little exercise have a greater chance of developing latent points. This is important, because some people feel that by restricting their range of motion, they are getting rid of their TrPs. Nothing can be farther from the truth.
Physical stress isn't the only thing that can cause TrPs. Tension TrPs can occur. These are not the psychological result of tension, but they are physiological biological effects of long term emotional abuse or mental trauma. If you are constantly holding your muscles tight in a "fight-or-flight" stress response, this changes your body patterns. When you have TrPs, muscle strength becomes unreliable. You may have also have noticed that if one part of your body turns over another while you sleep, the part being compressed goes numb. Some other symptoms include: stiffness, muscle tightness and weakness, localized sweating, tearing, salivation, poor balance, dizziness, nausea, tinnitus, goosebumps, runny nose, buckling knees, weak ankles, illegible handwriting, staggering gait, headaches, and muscle cramps.
“Secondary” trigger points develop when a muscle is subject to stress because another muscle with a trigger point isn't doing its job. Satellite TrPs develop when a muscle is in a referred pain zone of another TrP. Without proper intervention, and with perpetuating factors, the TrPs can lead to severe and widespread chronic myofascial pain (CMP).
CMP is not progressive. With proper intervention, these trigger points can be broken up and eliminated.
FMS and CMP are different syndromes. However, the vast majority of physicians lump them together because they see many patients with the FMS & CMP Complex. Unless doctors have a thorough knowledge of and familiarity with individual TrPs, they can't sort out the symptoms. One interesting difference between the two syndromes is that more women than men have FMS, but CMP affects men and women in equal numbers. Another difference is that muscles in locations that are some distance from the trigger points of CMP have normal sensitivity. In FMS, there is a generalized sensitivity.
FMS is, among other things, a systemic neurotransmitter dysregulation, with many biochemical causes. There are other problems as well, but they are all systemic in nature, such as the alpha-delta sleep anomaly. Chronic Myofascial Pain, however, is a neuromuscular condition. CMP happens because of mechanical failures -- the mechanics of physics, not biochemistry. Due to the nature of trigger points, some of the symptoms may seem to be systemic, but they are not. Initiating events, such as repetitive motion injury, trauma, and illness, can start a cascade of TrPs.