Understanding Oxidation and Reduction Reactions, Methylation and the Role of Glutathione, Vitamin B12 and Folate | Robert A. Erickson, M.D.
Most people have heard the term “oxidation” and from the sound of the word, may have developed the impression that it has something to do with oxygen. Indeed it does, because oxygen has a tendency to draw electrons to itself. This tendency, rather than the presence of oxygen itself, is actually what identifies oxidation. So oxidation is defined as a process in which a substance loses electrons. The oxidation of one substance is always accompanied by reduction, or the gaining of electrons on the part of another substance. Oxygen is essential to life, but oxygen is like fire. It needs to be kept in balance through antioxidants, known as “reducing” molecules. Hence the term “oxidation-reduction reaction,” also called a “redox” reaction. The two reactions are profoundly linked and we need both to survive.
The world is full of examples of this highly significant form of chemical reaction. One such example is combustion. An even more rapid form of combustion is an explosion. Likewise the metabolism of food, as well as other biological processes, involves oxidation and reduction reactions. So, too, do a number of processes that take place on the surfaces of metals: when iron rusts; when copper turns green; or when aluminum forms a coating of aluminum oxide that prevents it from corroding. If you take an apple and cut it in half, leaving it exposed to the air, the surface will turn brown. This is because it has become oxidized from the oxygen in the air. If you apply lemon juice, which is an antioxidant, on the cut apple surface, it will delay the oxidation process. Oxidation reactions are responsible for the spoiling of food, and to prevent spoilage, manufacturers of food items often add preservatives, which act as reducing agents.
Human Aging, Diseases and Oxidative Stress
Aging is a process of gradual oxidation, and our health as we age depends on successfully reducing excess oxidation. Numerous diseases are linked to high levels of oxidative stress – schizophrenia, depression, autism, chronic fatigue syndrome, fibromyalgia, heart disease, most chronic autoimmune and inflammatory diseases.
Oxidative stress in the arteries leads to atherosclerosis. LDL cholesterol, otherwise known as ‘bad’ cholesterol, it not really bad unless it becomes oxidized. Only then can it stick in the arteries. Measuring cardiac C-reactive protein (HS CRP) in the blood is a simple lab test that reflects oxidative risk in this regard. A level of less than 1 mg/L is associated with a low risk of cardiovascular disease and above 3 mg/L with a high risk. In the Harvard Women’s Health Study, results of the CRP test were more accurate than cholesterol levels in predicting coronary problems. Twelve different markers of inflammation were studied in healthy, postmenopausal women. After three years, CRP was the strongest predictor of risk. Women in the group with the highest CRP levels were more than four times as likely to have died from coronary disease, or suffered a nonfatal heart attack or stroke. This group was also more likely to have required a cardiac procedure such as angioplasty or bypass surgery than women in the group with the lowest levels.
As a person ages, oxidation can affect memory. Those senior moments when a person forgets a name or where they placed their keys can be a result of damage to the covering of nerve sheaths in the brain (called myelin sheaths). These nerve sheaths are like insulation covering an electrical wire, and when damaged by oxidative stress, nerve impulses and thinking can be affected. At the Center, there are various supplements we use to help repair this process.
Oxidation may also contribute to the development of cancer as oxygen molecules and other oxidizing agents (toxic metals, ionizing radiation, pesticides, etc), always hungry for electrons, extract electrons from the membranes in human cells. Over time, this can cause a gradual breakdown in the body’s immune system if this reaction is not balanced by removal of the toxins and/or intake of adequate antioxidants in the diet.
Glutathione is the Most Important Antioxidant
Glutathione is often referred to as the human body’s master antioxidant because of the numerous roles it plays. It is the body’s most abundant antioxidant. It performs a number of critical functions that center around detoxifying the body and boosting immune system function. Glutathione boosts immune function by supplying glutathione peroxidase to the red and white blood cells, preventing our blood from becoming damaged by free radicals. It also helps the body in the production of some killer cells which fight off certain diseases. It is very essential in protecting the body from the effects of excessive intake of alcohol and drugs, environmental pollutants, and toxins produced during the body’s metabolism. Glutathione keeps the liver, lungs and kidneys – our organs of excretions – healthy, but must be present in high concentrations in these organs as they are exposed to various metabolic and environmental hazards on a daily basis. Glutathione also helps prevent the build up of oxidized fats in the body. LDL cholesterol has a glutathione receptor site and adequate glutathione levels are needed to prevent LDL cholesterol from becoming oxidized and sticking in the arteries. Cigarette smokers have an increased risk of heart disease because of the high oxidative stress from the tobacco smoke and chemical additives overwhelming glutathione stores.
Glutathione is composed of three amino acids (protein building blocks) – cysteine, glycine and glutamate. The primary peptide needed to make glutathione in our diets is cysteine. You can get cysteine from eating meat, eggs, garlic, onions, red pepper, and other foods. Certain foods that contain gluten (found in grains such as wheat) or casein (milk protein) inhibit the uptake of cysteine. Wheat and dairy products contribute to chronic inflammation, according to some authorities. Many children with autism or adults with autoimmune disorders do better when they eliminate wheat and milk products from their diet. I would wonder if this is due to a redox reaction mechanism in addition to an allergic component. Of course, not everybody who eats dairy or wheat has poor antioxidant capacity. There are probably genetic factors that come into play. One of the tests we use at the Center to measure oxidative function is the Spectracell intracellular vitamin analysis. This unique test determines whether there is a deficiency of most of the main antioxidants such as glutathione, vitamin C, selenium, cysteine, lipoic acid, coenzyme Q10 and vitamin E at a cellular level. If you have not had a Spectracell study in the past 12 to 18 months, I suggest you call the Center at 352-331-5138 and schedule this lab test.
I.V. Glutathione = Rapid Response
The most effective way to rapidly boost glutathione levels is giving it intravenously in a short 30 minute IV. David Perlmutter, M.D., a Florida neurologist, pioneered the use of I.V. Glutathione therapy in his Parkinson’s disease patients. We have found most patients receiving a combination of I.V. Glutathione and all the B vitamins will rapidly feel calmer and less agitated, have improved mood and energy, and experience less malaise. This improvement at times occurs while the I.V. is going in, and usually within 24 hours. We use this therapy in our patients undergoing heavy metal detoxification, or who have had chemical exposures, adverse drug reactions, or anesthesia, or in whom we suspect the liver detoxification pathways are under stress. There are multiple oral glutathione products on the market, but since glutathione is a protein, it can be destroyed by our stomach acid. We do carry a patented form of oral glutathione complexed with phosphatidylcholine that is well absorbed and it’s destruction in the stomach much reduced.
Methylation and Oxidation-Reduction Reactions
Another process the body uses to stay healthy that is intimately linked to oxidation-reduction reactions is called methylation. When a substance is methylated it means a methyl group (CH3 molecule) has been added to it. Methylation is a broad and fundamental action that can regulate gene expression, protein function, and RNA metabolism. It can suppress viruses and even cancer viruses we are born with, and it helps us eliminate or detoxify heavy metals, and other poisons. In the liver especially, methylation helps change a toxic substance into a form of the compound that can be more easily processed and excreted by the body.
Methylation and glutathione are tightly connected and there is a metabolic crossroads where cells must decide to either make more glutathione or support methylation. The overall balance between these two options is critical to health. Too little glutathione and we end up with free radical, oxidative damage. Not enough methylation, and many genes will not be properly regulated and viruses suppressed. Excess homocysteine forms and the risk of atherosclerosis goes up.
How Vitamin B12 and Folate Fit In
Glutathione is needed to convert inactive forms of vitamin B12 into the active forms. The active form of vitamin B12 is Methylcobalamine. The active form of folate is methylfolate. Both are essential to the methylation process. Most B12 vitamin preparations contain cyanocobalamine, which is not active and is less useful than the active form for treating deficiency states. Some people have a genetic defect that doesn’t allow them to fully convert cyanocobalamine into methycobalamine. This is why at the Center we use a pharmaceutically compounded methylcobalamine for B12 shots, rather than the commercial cyanocobalamine. We also use oral supplements that contain 5 methyl-tetrahydrafolate. I should point out that we ourselves cannot make vitamin B12. Bacteria make if for us and since vegetables do not carry those bacteria, vegans can be deficient for B12. Also, as we age we can have more difficulty absorbing B12 from foods that contain vitamin B12 such as meat, fish, poultry, and eggs.
Methyl B12 is constantly recycled by the body. It donates its methyl group to homocysteine, which then turns into another amino acid, methionine. Once B12 is missing its methyl group, it needs to get a fresh one, and that’s where methylfolate comes in. When your level of methyl B12 is low, homocysteine builds up and this can cause heart disease and hardening of the arteries. Elevated homocysteine levels are also found in Alzheimer’s disease. Homocysteine levels are measured by a simple lab test.
Inflammation of the nerves is a complication of diabetes called diabetic neuropathy. It is a very painful condition. In a 2011 study reported in the Review of Neurological Diseases, patients with diabetic neuropathy were given a mixture of methyl B12, methylfolate, and the active form of vitamin B6 (pyridoxal-5’-phosphate). Tissue biopsies were taken before and after treatment with these vitamins. 73% of diabetic patients showed improvement on their biopsies and 82% reported reduced frequency and intensity of pain and numbness using this vitamin therapy.
Another study reported that patients with major depression responded to methylfolate in combination with antidepressants. In this 2011 study only 16.3% of patients responded to antidepressants alone while 40% with the combined therapy experienced major improvements. Another study at Harvard Medical School in 2009 demonstrated methylfolate by itself helped in reducing depression both in patients with low and normal folate levels. It also helped in elderly patients with dementia. This may be because folate is a necessary co-factor in the production of the neurotransmitters serotonin, dopamine and epinephrine. Methyl B12 and methylfolate may help some children with autism. In a 2009 research study of 40 autistic children treated with Methylcobalamine and folinic acid, there were significant increases in cysteine and glutathione after three months. Low levels of folate are also associated with anemia, heart disease, fetal abnormalities such as spina bifida, neuropathies and ADHD.
Two Case Studies with I.V. Glutathione and B Vitamins
Mr. P is a 66 year old patient who was originally diagnosed with prostate cancer in 1996. His initial treatment consisted of radical surgery of the prostate followed by post operative radiation therapy. In 2001 his PSA (prostatic specific antigen) lab test became elevated, indicating he had recurrent disease. He was treated with hormonal therapies. In 2011 is PSA shot up to over 50 and a CT scan showed metastatic involvement of his pelvis and lymph nodes. He underwent a series of 4 radiation treatments and since that time had been experiencing nausea, dry heaves, fatigue and general malaise. Mr. P also developed swelling in his leg (lymphedema) on the side of the radiation. He came to the Center to see me in January 2012 and it was felt that the fatigue, malaise and nausea were due to the radiation treatments rather than his cancer. Oral supplements to support his detoxification pathways and improve antioxidant status were begun. A series of I.V. Glutathione treatments with B vitamins at weekly intervals was also begun to reverse some of the oxidative stress from the radiation. The I.V. Glutathione was also used to improve liver and kidney function and to reduce his nausea. By the 4th treatment Mr. P started improving and by the 6th treatment his fatigue, malaise and nausea were virtually gone.
Mrs. J is a lady in her 40s who travels for her business. This past winter she contracted a flu-like illness during a trip out West where she had to fly on a commercial airplane and was exposed to multiple passengers who were coughing during the flight. Her symptoms upon her return were mostly head congestion, significant fatigue and malaise, chills, and low grade fever. Her sputum was not discolored and her physical exam, other than mild inflammation of the throat and ears, was unremarkable. When symptoms did not improve over the next week, she came to the Center. I felt Mrs. J had a viral illness and she was placed on ViraClear (a homeopathic product from Germany) and LDM-100 (an herbal product). Mrs. J was also given an I.V. with Glutathione 1000mg with B vitamins that included folate and Methylcobalamine. Within 3 days her symptoms resolved and she was able to return to her usual activities.
In a 2002 article published in “Free Radical Biology & Medicine,” the results of a joint study from Emory University School of Medicine and the Department of Microbiology and Immunology were presented. The study found that Glutathione has an anti-influenza activity both in cell cultures and in vivo in mice. Because infection by RNA viruses induces oxidative stress in host cells, the authors of this study concluded that cellular redox status plays an important role in regulating viral replication and infectivity. They went on to say that Glutathione therapy should be considered in addition to the usual strategies of annual flu shots and antiviral drugs in some at-risk populations.
Summary
Aging can be described as a process of gradual oxidation. Reducing the effects of free radical damage and oxidative stress is critical for health. The glutathione antioxidant system is a common target for so many different environmental toxins and infections and adequate glutathione levels keep us healthy by flushing out toxins and by boosting our immune function. The two B vitamins, folate and B12, are also essential in keeping a healthy oxidation-reduction balance. The body must be able to convert these two vitamins into the active forms so the body can methylate when needed and can make more glutathione when needed. Some of the functions of folate and B12 are production of DNA and RNA, protection against DNA mutations that might lead to cancer, prevention of anemia, protection against neuropathy, heart disease, depression, and high homocysteine.
[I would like to give credit to articles published in the October 2011 Focus Newsletter of Allergy Research Group for some of the data presented in this article.]