Oxidative stress is a major concern for those with ME/CFS. Here's a great primer to help you understand the different types of anti-oxidants and how they work. Dr Mercola mentions his faves are Resveratrol, Ubiquinol (the active form of CoQ10) and Astaxanthin (the bonus to using Krill Oil as an Omega-3 source). However, there's a new antioxidant in town with an extremely high ORAC score, that has at least one benefit over Resverartol in the anti-aging protein department - it's called 'Hydroxytyrosol' and is now available. Guaranteed you'll be hearing more about this one in the future! -Priya for ME/CFS Assist
By Joseph Mercola, MD • ProHealth.com • June 6, 2012
Nutrition expert Joseph Mercola, MD, greatly expands our understanding of free radicals, cell-damaging oxidative stress (typically elevated in ME/CFS and fibromyalgia), and antioxidants. First published May 16, 2011, this information is reproduced with kind permission from Dr. Mercola's educational website (Mercola.com). See footnote* for links to much more.
How a Normal Body Process (Oxidation) Can Contribute
to More than 60 Diseases
By now, just about everyone has heard of antioxidants and knows they are an important dietary component. Even many drug-focused Western physicians will acknowledge the importance of antioxidants for your health, at least in a general sense.
But do you know specifically what antioxidants are, what they do in your body, and what types you need?
• In this article, I will try to broaden your understanding of the group of nutrients known as "antioxidants," and hopefully increase your appreciation of their importance by helping you understand exactly what they do to keep you youthful and healthy.
• My secondary aim is to show why you need a wide variety of antioxidants to accomplish this goal, as opposed to taking mega doses of only one or two.
Antioxidants are crucial to your health, as they are believed to help control how fast you age by combating free radicals, which are at the heart of age related deterioration.
In his book The Antioxidants, Richard A. Passwater, PhD, explains how humans have one of the longest natural lifespans of the animal kingdom, and that this may in part be due to the wealth of antioxidants in our omnivorous diet. Our bodies produce antioxidant enzymes that are not found in many other creatures.
According to Dr. Passwater, "Our natural antioxidant processes compensate for one another, covering up momentary deficiencies by their overlap." Before we dive into antioxidants, you must first have a basic understanding of free radicals, because free radicals are what make antioxidants so essential to your health.
What Do Rotting Apples, Rusty Bicycle Frames, and a Sunburn have in Common?
Your body produces free radicals as a result of normal metabolism and energy production. Free radicals are a biological response to environmental toxins, such as cigarette smoke, chemicals, sunlight, cosmic and manmade radiation, and even a key feature of pharmaceutical drugs. Free radicals are also produced when you have inflammation in your body and when you exercise.
A free radical is a highly reactive metabolite missing one or more electrons - it has at least one unpaired electron. This missing election is largely responsible for the process of biological oxidation. These "partial molecules" aggressively look to replace their missing parts by attacking other molecules.
These reactions are commonly referred to as "oxidation" reactions. A bio-gerontologist named Denham Harman first discovered the concept of free radicals in 1954, while researching an explanation for aging. There is a duality to oxygen. Without it we would all be dead in a few minutes, however if we have too much it will damage our tissues.
Oxidation is like biological rusting and similar to what occurs to an iron bar that is dumped in the ocean.
You can also see evidence of biological oxidation after cutting into an apple and watching it turn brown from exposure to the air. The rust on your bicycle frame and the green patina on your penny are additional common examples.
Free radicals seek to steal electrons from many of the proteins in your body and can also result in damage to your DNA and other cell structures.
But it actually gets worse.
Free radicals can have a snowballing effect in which molecule after molecule steals from its neighbor, each one becoming a new free radical once it's been electron-robbed, leaving a trail of biological carnage...
Five Types of Free Radicals
Free radicals can be broken down into five types. The first four types come from oxygen atoms and are called Reactive Oxygen Species (ROS), but the fifth type derives from nitrogen:
1. Superoxide ion (O): An oxygen molecule with an extra electron that can damage mitochondria, DNA and other molecules.
2. Hydroxyl radical (OH): A highly reactive molecule formed by the reduction of an oxygen molecule, capable of damaging almost any organic molecule in its vicinity, including carbohydrates, lipids, proteins, and DNA. OH cannot be eliminated by an enzymatic reaction.
3. Singlet oxygen: Formed by your immune system, singlet oxygen causes oxidation of your LDL [low density lipoproteins].
4. Hydrogen peroxide (H2O2): Not a free radical itself, but easily converts to free radicals like OH, which then do the damage. Hydrogen peroxide is neutralized by peroxidase (an enzymatic antioxidant).
5. Reactive Nitrogen Species (RNS) (NO): Nitric acid is the most important RNS.
These various free radical species can damage DNA in different ways.
They can disrupt duplication of DNA, interfere with DNA maintenance, break open the molecule or alter the structure by reacting with the DNA bases. Cancer, atherosclerosis, Parkinson's, Alzheimer's disease, and cataracts are examples of diseases thought to result from free radical damage.
In fact, free radicals are implicated in more than 60 different diseases.
Lipids in cell membranes are quite prone to oxidative damage because free radicals tend to collect in cell membranes, known as "lipid peroxidation." (The lipid peroxide radical is sometimes abbreviated as LOO.)
When a cell membrane becomes oxidized by an ROS, it becomes brittle and leaky. Eventually, the cell falls apart and dies.
This is akin to what happens when butter, vegetable oils or meat becomes rancid - and why manufacturers sometimes add agents to prevent that. How can this free radical pillage be stopped?
This is where antioxidants come in.
Antioxidants are Your Body's Solution to Counter Excessive Free Radicals
An antioxidant is a molecule capable of inhibiting the oxidation of another molecule. Antioxidants break the free radical chain of reactions by sacrificing their own electrons to feed free radicals, without becoming free radicals themselves.
They are all electron donors.
Antioxidants are nature's way of defending your cells against attack by reactive oxygen species (ROS). Your body naturally circulates a variety of nutrients for their antioxidant properties and manufactures antioxidant enzymes in order to control these destructive chain reactions. For example, vitamin C, vitamin E, carotenes, and lipoic acid are well-known and well-researched antioxidant nutrients.
Your body can manufacture some of these antioxidants, but not others. And your body's natural antioxidant production tends to decline with age.
Fortunately, most of the vegetables you eat are loaded with potent phytochemicals that act as antioxidants. And the closer they are to being harvested, the more potent these antioxidants will be - which is why you should consume the majority of your fruits and vegetables RAW and locally harvested. If you eat vegetables that have been harvested weeks before, as is common in most grocery stores, you will not be reaping much of the potential benefit the food has to offer you.
Your body requires these important micronutrients to help you resist aging, generated by everyday exposure to pollutants in your food, water, and air. If you don't have adequate antioxidants to help squelch free radicals, then oxidative stress tends to lead to accelerated tissue and organ damage.
Oxidative stress can be defined as the state in which your free radicals outnumber your antioxidant defenses.
They can also serve to shorten your telomere length, which many experts believe to be the most accurate biological clock we have.
ORAC Scores a Tool to Help You Rate Different Antioxidants
Scientists at the USDA have developed a scale for measuring an antioxidant food or supplement's ability to neutralize free radicals, called ORAC score (Oxygen Radical Absorbance Capacity). The higher a food's ORAC score, the more powerful it is in combating age-related degeneration and disease.
If you want to look up an ORAC score, you can go to the ORAC value database. Keep in mind, however, that although ORAC can be a useful tool, some manufacturers have found a way to misrepresent ORAC values with deceptive practices which can lead you astray.
The best way to combat free radicals (therefore slowing aging down) is to make sure you get ample antioxidants in your diet. Your first and most important source will be from high quality organic locally grown whole foods. Wisely selected supplements have also been shown to be highly beneficial in addition to your food choices.
Enzymatic and Non-Enzymatic Antioxidants
Antioxidants can be categorized into two types:
1. Non-enzymatic antioxidants work by interrupting free radical chain reactions. For example, having vitamin E around may interrupt a chain of free radical activity after only five reactions, instead of its snowballing into 100 reactions. Non-enzymatic antioxidants include vitamin C, vitamin E, plant polyphenols, carotenoids and glutathione (GSH).
Glutathione has been called the “master antioxidant” and is found in every single cell of your body, maximizing the activity of all the other antioxidants.
2. Enzymatic antioxidants work by breaking down and removing free radicals. In general, these antioxidant enzymes flush out dangerous oxidative products by converting them into hydrogen peroxide, then into water, in a multi-step process that requires a number of trace metal cofactors (copper, zinc, manganese and iron). You can’t supplement these enzymatic antioxidants orally - they must be produced in your body.
Most antioxidants found in foods and supplements are of the non-enzymatic type. They boost your enzymatic antioxidant defense.
The principle enzymatic antioxidants are the following:
• Superoxide dismutase (SOD): Assisted by copper, zinc, manganese and iron, SOD breaks down superoxide (which plays a major role in lipid peroxidation) into oxygen and hydrogen peroxide. SOD is present in nearly all aerobic cells and extracellular fluids.
• Catalase (CAT): Converts hydrogen peroxide into water and oxygen (using iron and manganese cofactors), hence finishing up the detoxification process that SOD started.
• Glutathione peroxidase (GSHpx) and glutathione reductase: These selenium-containing enzymes help break down hydrogen peroxide and organic peroxides into alcohols, and are particularly abundant in your liver.
As you can see, these powerful enzymes do a wonderful dance in your body that turns toxins into harmless water!
Water-Soluble and Lipid-Soluble Antioxidants
Another categorization of antioxidants is based on whether they are soluble in water (hydrophilic) or in lipids (hydrophobic). You require both types to protect your cells.
• The interior of your cells and the fluid between them are composed mainly of water.
• But your cell membranes are made largely of fat.
• As you know, oil and water don't mix. Substances that are soluble in water are not soluble in fat, and vice versa.
• The lipid-soluble antioxidants (such as vitamins E and A, carotenoids, and lipoic acid) are primarily located in your cell membranes,
• Whereas the water-soluble antioxidants (such as vitamin C, polyphenols and glutathione) are present in aqueous fluids, such as your blood and the fluids within and around your cells (the cytosol, or cytoplasmic matrix).
• Free radicals can strike the watery cell contents or the fatty cellular membrane, so the cell needs defenses for BOTH.
• The lipid-soluble antioxidants are the ones that protect your cell membranes from lipid peroxidation.
The fact that antioxidants are so complex and multifactorial has led people to be confused about what antioxidants they should be taking. For example, I have been asked on more than one occasion if it's necessary for example to take a resveratrol supplement if you are already taking astaxanthin.
The short answer is, YES.
Astaxanthin is a lipid-soluble antioxidant, and polyphenolic compounds such as resveratrol [especially abundant in grape skins and seeds, red wine, and purple grapejuice], are water-soluble antioxidants. As you have now seen, each type has its own special function.
But solubility isn't the only variable among antioxidants.
Besides solubility and enzyme requirements, antioxidants also differ in terms of molecular size. There are small-molecule antioxidants and large-molecule protein antioxidants, which have different functions:
1. The primary function of the small molecule types is to mop up or “scavenge” the reactive oxygen species and carry them away through chemical neutralization. The main players in this category are vitamin C, vitamin E, lipoic acid, carotenoids, glutathione, and CoQ10.
2. The larger protein antioxidants tend to be the enzymes (SOD, CAT, O, H2O2, and GSHpx, outlined above), as well as “sacrificial proteins” that absorb ROS and prevent them from attacking your essential proteins. Albumin is an example of one of these sacrificial proteins, which “take the bullet” for crucial enzymes and DNA.
Clearly, biology has equipped you with a cornucopia of different defenses to cover just about every possible biological contingency.
A Myriad of Molecular Marvels
Besides interrupting free radical raids and melting down toxic invaders, antioxidants have some other unique and interesting functions, such as:
• Repairing Damaged Molecules: A few unique antioxidants can repair a damaged molecule by donating a hydrogen atom—and this becomes very important when the molecule is a critical one, like your DNA.
• Blocking Metal Radical Production (Chelating Effect): Toxic metals such as mercury and arsenic catalyze free radical production. Some antioxidants (such as green tea) have the ability to grab these metals and “hug” them so strongly that no chemical reaction can take place - and this is called chelation. Water-soluble chelating agents also help to escort toxic metals out of your body in your urine.
• Stimulating Gene Expression and Endogenous Antioxidant Production: Some substances have a remarkable ability to stimulate your body’s genes to increase your natural defenses. Whey proteins are thought to do this, as does exercise.
• “Shield Effect”: The flavonoids attach themselves to your DNA and protect it from attack by free radicals, acting as a virtual shield.
• Cancer Cell Suicide Promoter: Some antioxidants boost anti-cancer chemicals, halting cancer growth and even forcing some cancer cells to self destruct (apoptosis).
Exercise Can Help You Increase Your Own Antioxidants
In addition to your diet, exercise is an important part of boosting your body's endogenous antioxidant production in a paradoxical way. Exercise is actually a potent oxidative stress, but by doing wise amounts of exercise, such as short amounts of high intensity exercises like Peak 8, it will help improve your body's capacity to produce antioxidants.
Which Antioxidants Do You Need?
Let me emphasize that without question the most important way to optimize your antioxidant intake is to make sure you eat a large variety of locally grown fresh organic vegetables. Juicing is a convenient way to increase your intake, especially if you eat the pulp.
Additionally, reducing your sugar intake will decrease your antioxidant stress so that you will need less, and the ones that you have will work better and last longer. So resist sugars and processed foods.
You can also wisely select targeted nutrients to supplement your food choices.
I think Dr. Passwater says it best, so I will conclude with a passage from his book, The Antioxidants:
"Combinations of antioxidants are like a balanced symphony working together. A symphony orchestra produces sounds so much more harmonious than merely having 20 drums playing. It is not the quantity, but the blend. The same is true with antioxidant nutrients: you get better results with moderate amounts of a full complement than you get with using very large amounts of just one nutrient...
"For this reason, most of us in the field recommend that a person take a variety of antioxidants (a "cocktail"), not just a single substance.
"The importance of synergism is that the antioxidant nutrients each contribute to the total protection. They work together in the antioxidant cycle and reach all body compartments - fat and water-based, blood and internal cell. They protect against all types of free radicals and reactive oxygen species. No one antioxidant can do all of this."
Personally my favorites are:
• Ubiquinol (Co-Q10)
- Joseph Mercola, MD
By Jacob Teitelbaum, MD*
Over the years, people have often asked me for a list of my top 10 supplements - the ones to take if you don't have the funds, time or inclination to take more than a few and you'd like to be able choose those that give you the most "bang for the buck." Below I've listed my favorite 10 supplements, along with brief descriptions of each.
1. Energy Revitalization System - vitamin powder (Enzymatic Therapy)
One daily scoop of this supplement replaces over 35 tablets of supplements - talk about saving money and time! Use 1/2 to 1 scoop a day, whatever feels best to you. Blend it with milk, juice, water or yogurt, as you prefer. (Folks with blood sugar problems might want to skip the juice.)
If the supplement seems to trigger gas or stomach upset, mix the powder with milk and start at a lower dose, working your way up to the dose that feels best. Or divide the dose into smaller doses, taking it 2 to 3 times a day.
I formulated this product, which is available online and in most health food stores.
2. D-Ribose (Corvalen)
Ribose supplies the substrate of ATP, the body's main fuel. Use 1 scoop (5 gm) of powder, 3 times a day, for 3 weeks, then 2 times a day. (If you find the supplement too energizing, take it with food, or lower the dose.)
Most people see a boost in energy within 2 to 3 weeks of starting the supplement, and sometimes the first day.
A recent and very positive development: In our study of 257 patients with CFS/FMS, conducted at 53 health centers, those who took ribose saw a 61% average increase in energy after just three weeks. We've submitted the study for publication in a medical journal.
3-A. Revitalizing Sleep Formula (Enzymatic Therapy)
This formula includes: Valerian, 200 milligrams (mg); Passion Flower, 90 mg; L-Theanine, 50 mg; Hops, 30 mg; Piscidia, 12 mg; and Wild Lettuce, 28 mg.
Take 2 to 4 capsules every night, 30 to 90 minutes before bedtime. You can also take it during the day for anxiety. Don't take more than 8 capsules a day.
If the valerian energizes rather than relaxes you (which occurs in 5% to 10% of those who take it), take the other components of the formula as separate supplements.
3-B. Sleep Tonight! (Enzymatic Therapy)
Sleep Tonight is another sleep formula I like from Enzymatic Therapy. It's particularly helpful in people who feel wide awake at bedtime, a problem often caused by levels of the adrenal hormone cortisol that are too high at night, even if they're too low during the day. You can take it with the Revitalizing Sleep Formula.
You'll know if it these 2 herbal mixes are helping within 2 or 3 days - and usually after the first night of use.
They can be taken together and also along with other sleep medications.
Anti-Yeast Treatments 4. Acidophilus Pearls Elite (Enzymatic Therapy)
This probiotic supplement of "friendly" acidophilus bacteria delivers five times more probiotics than an earlier version of the pearls - which means you only have to take 1 a day, rather than 5, saving you time and money.
Probiotics that aren't in "pearl" form are doomed: 99% of them are destroyed by stomach acid before they ever reach your intestines, their site of therapeutic action.
5. Anti-Yeast (NutriElements)
This is an excellent mix of natural antifungals. Take it 2 times a day for 3 to 5 months. (Not currently carried by ProHealth)
6. Adrenal Stress End (Enzymatic Therapy)
This mix of adrenal glandulars, licorice and other key nutrients provides outstanding adrenal support. Take 1 to 2 capsules every morning (or 1 to 2 in the morning and 1 at noon).
7. Tri-Iodine (EuroPharma)
As I recently wrote in my new book, Real Cause, Real Cure - The 9 Root Causes of Most Health Problems, the intake of iodine has dropped by around 50% in the last 30 years, mostly because flour is now fortified with bromine rather than iodine.
In fact, bromine and other chemically related compounds added to food and water (the halides chlorine and fluorine) may actually block iodine.
The result: a little-recognized but very important recurring epidemic of iodine deficiency. And since iodine's main role is to manufacture thyroid hormones, an accompanying epidemic is hypothyroidism
Iodine deficiency also is a common trigger for breast tenderness and fibrocystic breast disease, and I routinely use Tri-Iodine in women with these problems.
Iodine is also low in women with breast cancer, and I routinely supplement the diets of my patients who have breast cancer with 6.25 to 12.5 mg daily.
A one-month trial of Tri-Iodine will be enough to tell if it's going to help you feel better. You can take either 6.25 mg or 12.5 mg capsules. However, don't take more than 12.5 mg a day unless you are doing so under a physician's supervision. And if you develop acne or indigestion after starting the supplement, stop taking it or lower the dose.
Pain - Two Outstanding Herbal Mixes 8. End Pain (Enzymatic Therapy, or End Fatigue Pain Formula by Integrative Therapeutics)
I developed both of these formulas. Each of them contains willow bark, boswellia and cherry. Take 2 tabs, 3 times a day. It takes 2 to 6 weeks to see the full effect. Once you do, you may find that you can lower the dose to 1 tab, 2 or 3 times a day (or as needed).
9. Curamin (EuroPharma)
This is a new and excellent natural remedy for pain. It contains boswellia, nattokinase and DLPA [an xx-amino acid]. But most importantly it contains curcumin, a powerful anti-inflammatory agent derived from the Indian spice turmeric (which gives curry its yellow color).
The problem with curcumin is that it's hard to absorb. Curamin solves that problem, by using a form of the compound (BCM-95) that is absorbed seven times better than 95% pure curcumin.
Curamin works very well in combination with End Pain.
The standard dose is 1 capsule, 2 to 3 times a day. For those with fibromyalgia, it's more effective to start with 2 capsules, 3 times a day for 6 weeks. Then return to the standard dose.
Chronic Sinusitis / Nasal Congestion
10. Silver Nose Spray (Natural Immunogenics)
Use 5 to 10 sprays in each nostril, three times a day, for 7 to 14 days, until the sinusitis resolves. (Not currently carried by ProHealth)
If your doctor will prescribe it, I strongly recommend adding the Sinusitis Nose Spray available from ITC Pharmacy [a compounding pharmacy; http://itcpharmacy.com]; your doctor can call 303 663-4224 or 888 349-5453.
- Jacob Teitelbaum, MD
by Mark J Pellegrino, MD*
July 6, 2011
Dr. Pellegrino is a leading fibromyalgia specialist and author who has had FM himself since childhood. His observations of familial fibromyalgia patterns and permutations such as "the aging threshold" reflect more than 20 years' experience treating patients at the Ohio Pain & Rehab Specialists Center. Basic knowledge to help genomic researchers sort things out as we move closer to understanding and control.
THE PROBABLE CAUSES OF FIBROMYALGIA
All of us involved in fibromyalgia, either by treating it or having it, have come to appreciate how complicated this condition is…. Most important, there is more than one way to get fibromyalgia; it is an “end point” condition with multiple ways leading to it.
One of my pet peeves is that I continue to read in the scientific literature statements such as “the cause of fibromyalgia is not currently known,” or "future research will hopefully discover the cause of fibromyalgia." This implies that we don't know anything about the causes. I have had some doctors and attorneys suggest to me that if the cause is unknown, then perhaps we are not even sure that fibromyalgia exists.
I think we can say that a number of causes of fibromyalgia are known at the present time. And I think one of our problems is that we try to be too scientific, when we really need to be more practical and logical. One difficulty is determining the difference between cause and pathological mechanism. In fibromyalgia the cause would be WHY fibromyalgia developed. The pathologic mechanism would be HOW fibromyalgia developed.
I have compiled a list of probable causes of fibromyalgia.
This list is based on my experiences and understanding of the current literature. My opinions on these probable causes may not be shared by everyone. My list of probable causes is as follows:
3. Connective tissue disease
5. Catastrophic stresses
6. Chemical exposure.
Probable FM Cause #1: GENETICS
These observations support the notion that fibromyalgia can be inherited, or at least the tendency to develop fibromyalgia is inherited:
• Physicians who see patients with fibromyalgia can recall a number of patients who are relatives.
• I have seen numerous family members,mother-daughter, sister-sister, sister-brother, etc., who have the typical symptoms and findings of fibromyalgia.
• Several members of my family have fibromyalgia through four generations!
• I also see numerous patients who tell me they have family members known to have it (their family history is positive for fibromyalgia).
• Many adult patients state they had pain as a child.
Several studies on the hereditary aspects of fibromyalgia have been published. Dr. George Waylonis and I published a study in 1989.(1)
We studied 17 families and as many first-degree relatives as we could gather up (sibling, parent, child), and concluded that:
• A number of family members had fibromyalgia in a pattern that suggested an autosomal dominant mode of inheritance. This means that if one parent has fibromyalgia, then 50% of the offspring have a chance of getting fibromyalgia, whether they are male or female.
• There also appeared to be a variable latent stage, which means that the fibromyalgia could develop at different ages in different offspring.
• There also appeared to be variable transmission (i.e., it could skip a generation).
My study found a high percentage of fibromyalgia in men with a positive family history, nearly equal to the women.
This is much different than the people who present to the doctor’s office, because among these people more than six times as many women as men will be diagnosed with Fibromyalgia. Men DO have Fibromyalgia, but they take a different course than women. Sometimes we have to go out and look for them because they do not tend to come to us to be diagnosed.
Dr. Dan Buskila from Israel performed a study looking at 60 children of 21 mothers with fibromyalgia.(2)
He found that 23% of the offspring, most of them female, have fibromyalgia. When he looked at the males with fibromyalgia, he found that the ones who were under 18 had fibromyalgia almost as frequently as the women under 18. He concluded that fibromyalgia had a major genetic component that possibly fit the autosomal dominant mode of inheritance (50% of children who have one parent with FM will have FM, whether male or female) - especially among males and females under age 18.
Dr. Buskila did another study looking at people with fibromyalgia, and many of their relatives.(3) He found that 45% of the relatives reported widespread musculoskeletal pain resembling fibromyalgia.
Other studies have supported an inherited pattern to fibromyalgia.
Dr. Muhammad Yunus performed Human Leukocyte Antigen (HLA) studies in fibromyalgia. HLAs are genetically determined molecules that are found in virtually all cells. HLA genes can be markers for certain diseases, and the results of Dr. Yunus’ HLA study suggests a genetic role in fibromyalgia.(4)
I believe that the literature, combined with accumulated clinical experience, supports a genetic cause of fibromyalgia.
A “common sense” approach would be to recognize that fibromyalgia is so common in the general population of the entire world that there must be some type of common genetic make-up that leads to it. Another logical conclusion from all of the available information is that people are genetically predisposed to getting fibromyalgia.
I think a number of people are programmed genetically to develop fibromyalgia over time, probably independent of the environment. However, for a number of others, an environmental trigger must occur (i.e., the other causes listed here and perhaps others yet unknown) for the fibromyalgia to develop.
Who Is at Risk Genetically to Develop Fibromyalgia?
I think the following can be considered at risk:
1. A child with one or both parents with fibromyalgia.
2. A child of one or both parents with a connective tissue disorder such as rheumatoid arthritis or lupus.
3. A child with a sibling who has fibromyalgia.
4. A child with a first-degree relative (parent or sibling) who has fibromyalgia.
Just because someone is a risk does not mean he or she will automatically get fibromyalgia. The right “trigger” may never happen. If a child at risk does become symptomatic with fibromyalgia, there’s a lot that can be done. (See
"Fibromyalgia in Children and Teens - Risk Factors, Symptoms, and Treatment"). Don’t assume that someone will get fibromyalgia or that it will be bad if he or she does.
Genetics Play a Role in Pain Sensitivity
Dr. George Uhl (a neurologist at Johns Hopkins) found that differences in pain perception were due to variations on the surface of nerve cells, specifically on the molecule called the mu opiate receptor. The mu receptor works by bonding with natural chemicals called peptides that help diminish the sensation of pain. Individuals who have lots of these receptors (too few mu’s!) cannot diminish the pain as well, and even small stimuli can cause severe pain.
The number of these receptors is controlled by the action of the mu opiate receptor gene. Those with fibromyalgia, or at risk for it, may be genetically mu deficient.
I believe with additional research we will be able to further clarify specific genes causing pain, identify gene expression profiles of specific subtypes of fibromyalgia, and develop genetic-specific medicines to control pain and reduce the effects of fibromyalgia.
[Note: just weeks ago, a pioneering study involving whole genome sequencing of identical twins with a rare condition found that they had inherited a "double dose" of such a gene variant, one from each parent; a "dramatic manifestation" of what in single copies the researchers believe may explain a recognized pattern of fibromyalgia symptoms among other family members.(5)]
Genetics and the “Aging Threshold”
A common story I hear from patients is that their pains gradually developed without any obvious or precipitating event. We mentioned earlier that genetics may cause some people’s fibromyalgia to develop randomly at some point, and once the pain starts it’s always there and can get worse over time. But is this process random, programmed, or subject to environmental factors? Probably a combination is involved.
I see many children and teenagers with fibromyalgia, but I see more adults in their 30’s or older when they first developed fibromyalgia symptoms. If genetics were the only factor in developing fibromyalgia, I would expect more younger patients with chronic pain complaints.
Genetic expression of a condition may take years to happen, so some people who first develop FM symptoms in their 30’s or later may have programmed genes causing the delayed expression.
Although genetics are a factor, I think there might be additional factors causing the “delayed” development of fibromyalgia; factors that I refer to as the “aging threshold.”
The aging threshold implies that as a person gets older, the threshold is lower for developing fibromyalgia. The person may be more vulnerable to getting fibromyalgia from various causes in the [probable cause list], but the aging process is also a risk for getting fibromyalgia, especially in women.
• Both men and women are found to lose their ability to inhibit chronic pain signals as they get older, and normal women already have a “defective” pain inhibitory system to begin with. Thus, any vulnerable person (who inherited fibromyalgia genes) would be less able to inhibit pain signals as he or she aged, and would become more susceptible to developing amplified pain (women more than men).
• Also, wear and tear changes on the body over time may contribute to the aging threshold. As we age, inevitably our muscles, tendons, ligaments, discs and joints show signs of deterioration accumulated micro-trauma. These deteriorating tissues may form painful areas, i.e., pain-generation. In a vulnerable person, the development of painful areas may trigger the “amplified pain” cascade.
• Additionally, hormonal changes over time can increase the risk for developing pain. For example, early menopausal women are more likely to report increased fibromyalgia pain.
If we combine these different factors, we can appreciate how the pain / fibromyalgia threshold lowers as one ages, and it appears that by the 4th or 5th decade (30’s and 40’s) the aging threshold has reached a “predictable” level - where fibromyalgia can take hold. Hence the increased frequency of fibromyalgia complaints in this age range.
Once the pain threshold drops below the body’s ability to inhibit potential / random chronic pain signals, the threshold is “breached.” Now, chronic pain signals have a better chance of propagating the amplified pain cascade of changes and lead to Fibromyalgia. (To read more on this cascade of changes, see “Fibromyalgia - Ultimately a Disease of Amplified Pain.")
Probable FM Cause # 2: TRAUMA
(See “Fibromyalgia as a Complication of Injuries.”)
Probable FM Cause # 3: CONNECTIVE TISSUE DISEASE
Many people get fibromyalgia associated with another disease, particularly rheumatic and connective tissue diseases. After genetics and trauma, I believe this type of disease is the most common cause of Fibromyalgia. Conditions in this category that can lead to reactive fibromyalgia include rheumatoid arthritis, lupus, polymyalgia rheumatica, and autoimmune disorders such as thyroiditis and Sjogren’s syndrome. Fibromyalgia does not turn into rheumatoid arthritis, lupus, or other inflammatory conditions, however.
Probable FM Cause # 4: INFECTION
(See “Infection as One Possible Cause of Fibromyalgia.”)
Probable FM Cause # 5: CATASTROPHIC STRESSES
These are synonymous with emotional trauma. These are not your everyday stresses. Rather they represent more severe stresses which can cause fibromyalgia. The mechanism is probably very similar to a physical trauma, only instead of a tissue injury, there is a stress injury that may disrupt the hypothalamic-pituitary-adrenal hormone regulation (the stress hormones).
Probable FM Cause # 6: CHEMICAL EXPOSURE
I’ve seen a number of patients who have developed fibromyalgia after chemical exposure. Usually they have inhaled fumes from offending chemicals which include petroleum oils, paint thinners, cleaning solvents, dyes, or gasses/fumes from burning products. Most of the time these patients are treated at the hospital, but have lingering symptoms and ultimately develop fibromyalgia. The mechanism whereby these chemical exposures cause fibromyalgia appears to be an allergic and/or autoimmune response that escalates and sets off the fibromyalgia cascade. Many people with fibromyalgia are sensitive to chemicals, drugs, and environmental allergens like pollen, dust and molds. A condition known as chemical sensitivity syndrome occurs when one becomes chronically fatigued and ill from exposures to various substances.
* * * *
We may not know the specific cause for a particular individual, but every single person with fibromyalgia has a cause, and ongoing funding and research of this complicated condition will result in further understanding. Future research will continue to shed light on these factors:
1. More specific identification of Fibromyalgia subgroups and better delineation of the overall Fibromyalgia Spectrum (See “The Fibromyalgia Spectrum - Part of the Big Picture in Understanding Fibromyalgia.")
2. Better understanding of the actual pathological mechanism, and learning what specifically triggers fibromyalgia from a microscopic or cellular level.
3. The ability to predict who will get fibromyalgia and what happens over time, and to understand the risks.
4. Additional genetic research to identify specific gene markers or specific neurobiological factors that contribute to fibromyalgia. Genetic research could also identify healing factors or specific gene therapy.
1. "Familial occurrence of primary fibromyalgia," Archives of Physical Medicine and Rehabilitation, Jan 1989.
2. "Mechanisms of Disease: Genetics of Fibromyalgia," Nature Clinical Practice, Rheumatology, 2006.
3. "Epidemiology of Fibromyalgia," Current Pain and Headache Reports, 2003; "Genetics of Chronic Pain States," Best Practice & Research, Clinical Rhematology, 2007.
4. "Genetic linkage analysis of multicase families with fibromyalgia syndrome," Journal of Rheumatology, 1999.
5. "Will Gene Variant Discovery Explain Fibromyalgia?"
* Note: This article is excerpted with kind permission from Dr. Pellegrino’s book, Fibromyalgia, Up Close & Personal © Anadem Publishing, Inc. and Mark Pellegrino, MD, 2005. You may purchase a copy of this highly recommended book by contacting Dr. Pellegrino's office at the Ohio Pain & Rehab Specialists Center (Phone: 330-498-9865, Toll-Free: 800-529-7500).
A Simplified Methylation Protocol is Effective for the Treatment of Chronic Fatigue Syndrome and Fibromyalgia
by Neil Nathan, MD
May 11, 2011
Reporting on an important trial to determine whether FM and CFS patients are affected by compromised methylation ability, and whether nutrients the body employs in methylation might support improvements.
Dr. Neil Nathan is a noted specialist in integrative treatment of complex medical illnesses such as fibromyalgia, chronic fatigue syndrome, and Lyme. In addition to his clinical work with Gordon Medical Associates near Mendocino, CA, he is a respected educator, and author of the new book, On Hope and Healing: For Those Who Have Fallen Through the Medical Cracks.
Dr. Nathan invites reader questions regarding the protocol he describes below. To submit a comment or question, click HERE, and watch for the resulting Q&A later this month on ProHealth.com.
I suspect that the words "methylation protocol" are, at first glance, intimidating. But if you will hang in with me for a few paragraphs, I would like to make this both understandable and useful.
First of all, what is most important is that we have recently shown that the use of tiny doses of very specific combinations of vitamin B-12 and folic acid has resulted in significant improvement in patients with fibromyalgia and chronic fatigue syndrome. That's the bottom line.
So, if you are suffering with chronic fatigue syndrome and/or fibromyalgia, you may be interested in learning more about our research, and what we learned.
Let's start with the word "methylation" and de-mystify it.
In chemistry, a methyl group is simply a carbon atom surrounded by 3 hydrogen atoms, which chemically looks like this:
C - H
This grouping acts as a unit and if we tack this unit, this methyl group, on to another molecule, that is what we mean by methylation.
You don’t need to be a chemist to understand that this process of methylation is absolutely critical to a host of the most important chemical reactions in our bodies.
Most important is that we need methylation to:
• Create glutathione (the body's 'master' antioxidant and detoxifier)
• Produce energy
• Impact brain chemistry
• Repair DNA
• And make melatonin from serotonin
These are only a few of the essential reactions that require our ability to methylate.
Genetically a Bit Compromised
What we have recently begun to understand is that many of us are genetically a bit compromised in our ability to methylate…
And that when we get sick that adds another dimension of difficulty to our illness, one that we can no longer compensate for.
What we have also begun to understand is that we can fix this. By taking a combination of what are essentially vitamins, we can bypass these genetic “blocks” to methylation, and restore the body’s normal chemistry.
This concept was pioneered by Amy Yasko, PhD, who was working primarily with autistic children.
She found that with treatment of methylation blocks many autistic children recovered to a remarkable extent. She suspected that other illnesses, such as chronic fatigue syndrome, fibromyalgia, Parkinson’s disease and other neurodegenerative diseases had a similar problem.
Rich Van Konynenburg, PhD, a biochemist, picked up on her concept and applied it to chronic fatigue syndrome and fibromyalgia.
In a series of papers, he demonstrated that virtually every known biochemical imbalance known to occur in fibromyalgia and chronic fatigue syndrome could be explained by this inability to methylate properly.
Hearing Rich’s lecture in 2007, and having a huge practice of fibromyalgia and chronic fatigue syndrome patients, I was excited to try out this hypothesis on some of my sickest patients. These patients had not fully responded to the treatment program pioneered by Jacob Teitelbaum, MD, which I have utilized for over 15 years now.(1)
As soon as I got back to my office, I gave 50 patients this combination of B-12, folic acid, and vitamins(2) recommended by Dr. Van Konynenburg, which was based on recommendations from Dr. Yasko.
To my delight, 70% of my patients had improved within 3 months, and 20% reported that they were much better, occasionally to the point of feeling cured.
This was exciting news. I was fortunate enough to obtain a private research grant to do a more formal study. With the assistance of Dr. Van Konynenburg and Dr. Yasko, along with input from Dr. Teitelbaum, who helped design the data collecting research tools, and Dr. Richard Deth, a well-known expert on methylation chemistry, we put this together.
The Project Went as Follows
• I took 30 patients (none of whom were part of the first pilot project), all of whom I had treated with Dr. Teitelbaum’s program, all of whom had made some progress (ranging from 30% to 70% improvement) but were still not where they needed to be health-wise.
• All had their methylation chemistry measured prior to the start of the supplements(3), and all took the supplements for the next 6 months, while we measured their chemistry and they reported on their health status throughout. All patients took exactly the same supplements.
• After six months, we individualized the patients’ treatment program based on their chemistry results, and continued to follow their progress and monitor their chemistry.
The Results Are Exciting (4)
Several important questions are addressed and answered:
1. First of all, do we find that fibromyalgia and chronic fatigue patients do, indeed, have abnormal methylation chemistry? YES
The initial methylation testing showed that:
• Every single patient had abnormal results.
• The average starting value of glutathione in our patients was 3.2 mmol/L (normal being 3.9-5.5 mmol/L)), and the average starting value for SAM (S-Adenosyl methionine, aka SAM-e, the major methylator) was 218 mmol/L (normal being 221-256 mmol/L).
• 83% started with low glutathione levels.
2. Can we demonstrate that taking these supplements raises those numbers into the normal range? YES
• After 3 months, the average glutathione level was 3.8 mmol/L
• After 6 months, the average glutathione level was 4.3 mmol/L
• After 9 months, the average glutathione level was 4.7 mmol/L, which represents a 47% improvement, and ALL patients now had a normal level.
• After 3 months, the average SAM level was 227 mmol/L
• After 6 months, the average SAM level was 238 mmol/L
• After 9 months, the average SAM level was 241 mmol/L, with only one patient not up into the normal range.
3. Does this rise in glutathione and SAM correlate with clinical improvement? YES
We had our patients rate 5 important areas of function on a 1-10 scale. This included energy, sleep, pain, cognitive function (memory, focus, concentration, and “brain fog”), and overall sense of well being.
We can demonstrate progressive improvement in all of these areas in most patients, over the 9 months of the study:
• Sleep improved from an initial score of 4.7 to 6.0, with 73% of patients reporting improvement.
• Energy improved from an initial score of 3.9 to 6.6, with 86% of patients reporting improvement.
• Pain improved from an initial score of 5 to 6.6, with 80% of patients reporting improvement.
• Cognitive function improved from an initial score of 5.0 to 6.3, with 73% reporting improvement.
• Overall sense of well being improved from 4.3 to 6.8, with 79% reporting improvement.
4. How much better were our patients? A LOT!
It took an average of 5 to 6 weeks before the supplements started to work, and we can clearly show that the longer patients stayed on this program, the better they got.
• Not everyone got better, but the vast majority (86%) improved.
• The average improvement was rated by our patients as 48%.
• And notably, 27% reported so much improvement that they now felt essentially well! Several who had not worked in over 5 years were able to resume full-time employment without difficulty.
In doing a study of this sort, we must look at how many patients completed the study so that we know whether these numbers are valid. (The data for improvement in glutathione and SAM has a p value of <.05, which is quite statistically significant.)
Of the original 30 patients, all 30 completed the first three months; 29 completed the first six months; and 25 of 30 completed the full 9 month program.
It is rare to conduct a study this long, with this type of compliance. It is also interesting to look at those who dropped out of the study. Three dropped out because they were so well that they saw no point in continuing. One dropped out because she needed to have bilateral hip replacement, and one dropped out because she did not feel any better after 6 months.
Protocol Supplements are Very Safe, But Medical Supervision is Essential
I would like to emphasize that the natural supplement components of this protocol are really very safe, with virtually no known side effects.
However, when we do, indeed, improve the body’s ability to methylate and make more glutathione – that is, when the nutrients work – they may improve the body’s ability to detoxify, thereby creating a toxic load that the body can’t handle. This may lead to a detoxification reaction which can range from mild to severe, making those patients quite ill.
I recently talked with Dr. Patricia Kane, PhD, (director of the nonprofit NeuroLipid Research Foundation) about this, and she believes that the protocol may release toxins bound to cell membranes, which sets this reaction off.
So it is imperative that patients find a knowledgeable health care provider to work with who understands this, can adjust the protocol to their needs, and help them get around that reaction if it occurs.
And importantly, if an individual gets worse in any way after starting the methylation protocol, they should stop, immediately. Continuing the protocol without supervision has made a number of patients very, very ill and I really would hate to see that happen to anyone.
For More Information
The details of this study, along with a much longer description of methylation chemistry is available in my new book, On Hope and Healing: For Those Who Have Fallen Through the Medical Cracks
The book also contains a description of the entire biochemical underpinning of chronic fatigue syndrome and fibromyalgia, in what I hope is a readable and concise format. This includes discussions of adrenal, thyroid, sex hormone imbalances, deficiency of magnesium and amino acids, food allergy, intestinal dysbiosis, toxicity from heavy metals, mold, and infectious agents such as Lyme disease and chronic viral infections.
- Neil Nathan, MD, May 2011
If You Have Questions for Dr. Nathan
Please submit comments and questions for Dr. Nathan HERE and watch for the resulting Q&A with his responses later this month on ProHealth.com.
Note: Some nutrients mentioned in this article may be available in the ProHealth store. If you have questions, the Customer Service Staff is always pleased to help.
1. I am referring to Dr. Teitelbaum’s SHINE approach to treating CFS & FM in toto (Sleep, Hormones, Infections, Nutrition, Energy), as outlined in his book, From Fatigued to Fantastic. To me, this means evaluating and treating adrenal, thyroid, sex hormone, magnesium, dysbiosis, candida, heavy metal toxicity, infections,and mold toxicity in its fullest scope. Dr. Teitelbaum was with me when we put together the methylation research, helped with developing some of the forms we used, and subsequently publicized the findings.
2. Though lots of people have lots of other ideas on nutrients that can be included in the protocol, most of that is speculation. All we can say with any degree of accuracy is that the protocol we used works - and for our international readers, most of the ingredients will be available to them as a starting point.
The essence of the simplified protocol that we used – the ingredients that I view as central to the protocol – are:
• The B-vitamin folic acid (specifically including the two most bio-available forms of folic acid - 5-methyl tetrahydrofolate, and 5-formyl tetrahydrofolate),
• And several types of B-12, of which the hydroxycobalamin type is the main ingredient.
• Then, the addition of Dr. Yasko’s multivitamin-mineral added a number of co-factors which are important. Formulated for her autism patients, this “Neurological Health Formula” includes antioxidants, trimethylglycine, nucleotides, supplements to support the sulfur metabolism, a high ratio of magnesium to calcium, and no iron or copper.
Phosphatidyl serine, included in some versions of the protocol, is helpful, but not central.
And there are two supplements associated with some methylation protocol versions that we do NOT use, at least initially:
• We have some doubts about using glutathione, since taking it gives the body the wrong message about how much it has available, and may, in fact, give the body the wrong message so that it stops making it properly. So, although I do use glutathione in a variety of circumstances, I believe that stimulating the body to make it, as in our protocol, is a much wiser approach.
• Similarly, we may use SAMe, but not initially, for the same reason.
3. The best methylation test (the one we used in our study) is simply called a "methylation panel" from Vitamin Diagnostics Lab in New Jersey. It runs about $325 for 11 measures of methylation chemistry, so it would be cheaper to just start the protocol, which is what I advise. I don't typically order the panel unless the patient is not responding to it adequately, so we can figure out what they are missing.
4. As described in the paper titled “Treatment Study of Methylation Cycle Support in Patients with Chronic Fatigue Syndrome and Fibromyalgia,” by Neil Nathan, MD, and Richard A Van Konynenburg, PhD. Presented at the March, 2009 International IACFS/ME Conference in Reno, Nevada.
Note: This information has not been reviewed by the FDA. It is general information, is not intended to take the place of personal attention by a medical professional, and is not intended to prevent, diagnose, treat, or cure any illness, condition, or disease. It is very important that you make no change in your healthcare plan or health support regimen without researching and discussing it in collaboration with your professional healthcare team.