Using inositol for promoting brain wellness: an interview with Robert Belmaker, MD

Robert Crayhon: Joining us now to discuss his groundbreaking research on inositol and mental health is psychiatrist and researcher Robert H. Belmaker, MD. Dr. Belmaker, would you please give us your educational background?

Robert Belmaker: I received my Bachelors Degree in 1967 at Harvard University and my MD in 1971 at Duke University. I then started a psychiatric residency at Duke and then went to the National Institutes of Mental Health as a clinical associate from 1972-1974. I then came to Israel in 1974 and completed my psychiatric residency. Eventually, I became director of research at the Jerusalem Mental Health Center in Jerusalem. Later, I became in addition, an associate professor of psychiatry at the Hebrew University School of Medicine in Jerusalem. In 1985 I came to the new medical school in Beersheva at Ben Gurion University to become the Hoffer-Vickar Chair of Psychiatry.

RC: Can you just describe for us briefly, your daily duties?

RB: I am a professor of psychiatry; I am the assistant director of the Beersheva Mental Health Center, so I have administrative duties. Every Monday I have a full clinic day with my own patients. Sometimes with my own 30 patients. Two to three times a week I do rounds on inpatients with the residents as well. So I have clinical, teaching and research duties.

RC: What got you interested in the role of nutrition in brain function as a psychiatrist?

RB: I think it's partly derived from some skepticism about the pharmaceutical companies. It is also derived from the feeling that so much of what we ingest everyday is food, and that chemicals in food must have some effect on our brain, and perhaps some potential therapeutic effects on the brain. But actually the chair of psychiatry that I am incumbent of was endowed by a family that has been famous for their interest in nutrition and psychiatry. I haven't decided to this day whether they found me and endowed the chair, or whether the endowment of the chair influenced my thinking. But, of course, Abram Hoffer, MD, PhD, from Canada has been interested and influential in nutrition and psychiatry for fifty years now. He published in the 1950s about nutrition and psychiatry when it was very unpopular, and he very bravely continued.

RC: Is the connection between nutrition and psychiatry any more popular now in psychiatric circles?

RB: There is an increase in interest in nutrition and psychiatry. However, like the increased interest in nutrition and medicine, it goes with a healthy degree of skepticism. There are a fair number of people who are suspicious -- perhaps sometimes rightly so -- of excessive claims. Often people with severe mental illnesses reject any drug treatment. They do that partly because of their illness in their thinking. Sometimes they use arguments derived from the nutrition literature and don't get proper pharmaceutical treatment. This is a shame, and this makes some psychiatrists in this position skeptical about nutrition. Clearly, however, some patients with heart disease need surgery and sometimes need triple artery by-pass, and other patients with high blood pressure are clearly going to need hypertensive and anti-hypertensive medicine. All cardiologists today know and believe and preach the role of nutrition in preventing heart disease and high blood pressure. So, the two should not be seen as antagonistic. In psychiatry there is no question that the anti-psychotic drugs and the mood stabilizer drugs are effective. But I think perhaps we are a little behind cardiology and some of the papers show that folate supplementation can enhance the ability of lithium to prevent mood disorders and the ability of anti-psychotic drugs to reduce psychosis. These papers are not given as much publicity and as much acceptance as they really deserve. I don't know if it's because they do not have a pharmaceutical company pushing folate -- because it's too cheap -- or whether it's the skepticism that might be a result of excessive claims of the past. Or perhaps it is the skepticism that is coming as an antidote to the fact that some patients refuse pharmaceutical treatment, and only want natural treatment. Often those patients are too sick to be able to make a rational decision.

RC: Dr. Belmaker, do you feel the future of psychiatry is an intelligent integration of pharmaceuticals and nutrients? And, should nutrients be tried first?

RB: I think we have to answer that question empirically. There are going to have to be studies, like the ones we did with inositol. There is no way to know what comes first and what comes second. Certainly in most cases nutrients are milder. If a person finds changing his diet can prevent his headaches, we would like to see him do that before he tries a strong medicine like Valproate to prevent a headache. Ultimately, it has to be an empirical question. We have to do the studies.

RC: What got you interested in inositol?

RB: I had been interested previously in lithium and I am still interested in lithium. As you know, lithium is a very simple compound and a non-patented compound and a cheap compound. Those are some of the things that keep my interest. I have been interested in lithium for 30 years. Lithium has a major effect on inositol and the brain that was discovered by a wonderful man, name of Dr. Berridge from London, a Nobel prize candidate for that work. That work was done on flies, of the salivary gland of the fruit fly. For those people who sometimes make jokes about how animal research is not relevant, here is an example of how something that seems terribly funny, the salivary gland of the fruit fly, has become a major area of scientific research, with many important benefits for humanity. He discovered the whole cycle, the inositol cycle of the cell, and that lithium had an effect on it. So, as a lithium researcher, I read his papers and got interested in inositol. Professor Berridge was very interested in how inos itol can affect cell function. We were really the first to think that one could possibly give inositol as a nutrient in quantities that could get it to the brain.

RC: How does lithium affect inositol's function?

RB: It's a bit complicated, and there are still disagreements about it. Lithium inhibits a key enzyme called inositol mono-phosphatase. Some people say, as a result, inositol levels in some areas in the brain should go down. Other people believe because that enzyme is inhibited, the inositol phosphates actually go up, and we really don't know which of those two things are more important in lithium action.

RC: What is the difference between inositol and myo-inositol? Is there a difference? Is it just two terms for the same thing?

RB: For a biologist they are two terms for the same thing. The only inositol that exists naturally in the body of the human or any other mammal is called myo-inositol. For a chemist, inositol can exist in eight different forms that are mirror images of each other, although it might be hard to imagine how you can have eight different mirror images; but that's because there are eight different places on the inositol molecule that a carbon and a hydroxyl group can have a mirror image. But, only the myo-inositol is present naturally so when I talk about inositol as a medicine or a cell, I can just drop the myo and call it inositol, because that is the only one that we have.

RC: What happens when the human body is given inositol orally?

RB: It depends on the dose. The doses that we found are large enough to get inositol into the brain are the dose equivalent of 3 to 6 teaspoons a day. That's 12 to 18 grams. It could be teaspoons in tea or in juice. That's the quantities that we are talking about. In order for these doses to be effective, they need to be taken over a period of three to four weeks. We found those doses to be as beneficial as anti-depressants used in depression, panic disorders and in obsessive-compulsive disorders. We've done one study in normal volunteers, who were given a much larger dose at a single time in the morning in a large cup of juice. They were given 12 grams in one swallow and then every hour they were asked to fill out rating scales as to their tension, mood, feelings of relaxation, feeling of wellbeing, welfare, things that a normal person would write, called a profile of mood scale (the scale for normal mood), and we found that indeed, even a single dose peaking at about six hours reduced tension and increased feelings of well-being. In depressed patients we don't see those effects quite so early. Perhaps because the depression is strong enough to mask them, and in these patients, inositol did not work any faster than standard antidepressants. It only had a significant and beneficial effect after about three weeks.

RC: How does inositol work?

RB: That of course is a very good question. We have done quite a bit of animal work in rats to look at the mechanism and we think that the strongest findings relate to serotonin and particularly the 5HT2 serotonin receptor. In a rat if you drip serotonin on neurons with those receptors, and measure the response, after a while the nerve cell stops responding and if you add inositol it jumps up and starts responding again. So, it seems like cells can get depleted of inositol. Or, specific nerve cells might not have enough to be able to maintain neurotransmission in the serotonergic system. Of course, there are many things we have not investigated, but it could be that some patients have deficiencies in the brain of inositol to the point where their serotonin system cannot respond.

We did do a study with brains donated after death from patients with depression, manic-depression and other mental illnesses, and no illness. These were given to us by the Stanley Research Foundation in Washington DC, which was able to obtain these brains from people who consented before their death to donate their brains. They were diagnosed before their death as suffering from these diseases. We did find a group of patients especially with affective disorder with low, very low inositol levels in the brain.

RC: Is there a way for most people through their diet to get enough inositol? When you are talking about a therapeutic dose in the 12-18 gram range, I am wondering where someone may get a gram of inositol on a daily basis though food.
RB: The usual intake is about a gram a day through food. I think it would be really hard to get 12 grams a day through food, I think that is really a pharmacological dose. Of course, prevention of depression might require a lower dose, and we have been interested. I have a colleague now, a dietitian, whom I have asked to do some surveys of the diet of people who come complaining of depression, to see whether there are different amounts of inositol. We also have a study that will be published in May in the American Journal of Psychiatry on omega-3 fatty acids, another nutrient that we found to be anti-depressant in depressed patients, and on this we were not the first.

RC: Has there been an actual clinical trial of omega-3 fats in depression?

RB: Let me just say one thing about the omega-3s. There is one previous study by Andy Stull of Boston, a Clinical Trial with positive results. What I wanted to say is that the omega-3s also are given in much higher doses than are present in the usual diet, even though there have been reports of a correlation in the usual diet, such that the people who eat more omega-3s get depressed less. It might be with some of these nutrients you need more to correct real depression than you do to prevent it.

RC: Which will bring us back to a lesson taught to us by Abram Hoffer decades ago -- that is exactly the case. If you are missing a nutrient for decades you might need a lot more for the rest of your life to get back to normal. Regarding inositol and the diet, my understanding is that inositol in our food is largely in the form of inositol hexaphosphate, which is in a form of fiber that's hard to absorb. In other words, it might be in the food, but how well we absorb it, I think is perhaps open to question.

RB: I think you are asking a very good question, it's something I am just getting very interested in, and don't have the answer for you.

RC: Let's talk about inositol in some other applications, to say it's effective in depression at doses of 12-18 grams, but you've got to give it three weeks to really see the results?

RB: That's right.

RC: What about agoraphobia?

RB: We tend to call this panic disorder, with or without agoraphobia. Same doses seem to be effective, and also our statistical significant results occurred at three weeks. There was a strong trend before that, but our statistical significant results occurred at about three weeks.

RC: What about obsessive-compulsive disorder and inositol?

RB: In obsessive-compulsive disorder our studies use 18 grams. I can't say it doesn't work less than that, the way it works with depression with 12 grams, but we just haven't tried it. These people tend to be more ill -- and started with 18 grams. We've only seen statistically significant improvement by about six weeks, not before that. It does take longer, which is similar to drug treatment for obsessive-compulsive disorder.

RC: And only with inositol monotherapy, with no other nutrient or drug?

RB: That's right.

RC: Very impressive. Did you arrive at these doses by clinically examining the fact that the 3 and 6 grams doesn't work and then titrating upward to 18 grams?

RB: We arrived at the doses actually first with the pharmacokinetic studies. We tested to see what doses were necessary to get a good rise in inositol in human spinal fluid. Less than 12 grams a day didn't achieve much of a rise. At 12 grams a day, there is a 70% rise in human spinal fluid inositol levels. We have tried some patients in the early days more than now on lower doses, so we had some feeling of what the dose should be. I must say it has not been done in a systematic way because these kinds of controlled trials are expensive. We haven't had the funding that the pharmaceutical companies have. To really work up inositol in the way you are describing with very large trials in multiple doses -- is a one hundred million dollar project. No one would give us this to study a non-patentable compound. We had some grants from NIH and from the Stanley Foundation, but we have not done a good dose response study.

RC: What about SSRI medications and inositol, since they seem to be accentuating the same pathway. What if someone is taking a Zoloft or a Prozac and they ask their physician, "Can I take inositol at the same time?"

RB: We have studied that, and we have not had side effects with it. But, to our surprise and disappointment, we did not see synergism. We would have hoped for synergism, but it seems that inositol works and the SSRIs worked. If you put the two of them together it doesn't work any better than inositol alone or SSRIs alone. So that SSRIs in that sense are an alternative to inositol, or inositol is an alternative to SSRIs. We don't have reason to believe that it is a good addition to a SSRI non-responder, although we have not found it in any way unsafe if someone wants to try.

RC: What if someone wants to transition off of a SSRI? Would inositol be a logical stepping-stone to perhaps a more natural approach to accentuating serotonin metabolism?

RB: It is certainly an option, but we don't have data on that. We have data on people who have been treated in the past with SSRIs successfully and on their next depressive episode they were treated successfully with inositol. But we don't actually have people going from one to the other in the same depressive episode.
RC: Let's talk about inositol and safety. You've used doses of 18 grams in your trials and your practice. Any side effects from these doses?

RB: Well, people will have some loose stools and about the same with some of the SSRIs. I would say about quarter of the patients will move their bowels more frequently. We've had very few people who have to stop the medicine for that reason. We have not seen any significant changes. By now we've have a fairly large number of patients with hematological or chemical parameters. This is a large number of patients for a natural compound, but these are still fewer patients than would be expected, let's say for the FDA. If it were a new SSRI, they would want a considerably larger number of patients.

RC: Is there anyone who should not take inositol?

RB: I think it would make sense for someone who was diabetic to be careful. Someone with severe kidney disease or liver disease to be careful with inositol but I think this is a very general medical consideration.

RC: And that's because inositol has a molecular similarity to glucose and because of this theoretically could raise blood sugar in diabetics?

RB: That's right.

RC: Any other pearls here for nutritional pharmacology research? You spoke about folate and omega-3s, any other information you would like to share with our readers?
RB: Well, I think one of the most exciting things that we've been doing lately is with homocysteine. Homocysteine is the amino acid that's not used in protein synthesis and its been shown to be a risk factor for cardiovascular disease over the last few years. In more recent years it's been proven to be a risk factor for Alzheimer's and cerebral vascular disorders as well. We thought that this might mean that it's a risk factor for mental disorder and we have been surveying homocysteine levels in our patients and have found markedly elevated levels of homocysteine. We have begun a trial of folate, B12 and B6 in schizophrenic patients, because these are known to be homocysteine lowering vitamins that can lower homocysteine levels by up to 50% in combination. Homocysteine has been shown in a test tube to be neurotoxic, so we think we might be able to prevent the clinical deterioration and cognitive deterioration in schizophrenia with homocysteine lowering.

RC: Have you seen lowering homocysteine to be an effective strategy; perhaps in the treatment of depression?

RB: We have not looked at that.

RC: What happens when you give a patient a good-sized powder container of inositol and say "Take 6 teaspoons per day, please." Do they look at you and say "why is this doctor giving me a nutrient, and so much of it?"

RB: Well, I explain it. Most of the patients that consent to be on our program are people who are looking for this. That's how they get to us. So we find it very acceptable among patients, compliance is very high.

RC: Does it matter if inositol is taken with food or not?

RB: No it doesn't. It's absorbed very well. We recommend it be taken with some food

Metagenics Cenitol Powder with Inositiol

Fish Oils and Mood Disorder Prevention

Metagenics EPA-DHA Extra Strength® Concentrated and Stabilized Purity-Certified, Omega-3 Fish Oils EPA-DHA Extra Strength is a concentrated source of health-promoting, antioxidant stabilized, omega-3 essential fatty acids from cold water fish. EPA-DHA Extra Strength supports healthy musculoskeletal, cardiovascular, nervous, and immune functions.

Advantages of this premium formula include:
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Fish Oils and Mood Disorder Prevention
In addition to adequate micronutrient intake, fatty acid balance also plays a critical role in mental health. Low fish consumption has been found in multiple studies to be a statistically significant finding in those with depression. For example, this study showed that rates of depression increased more than twofold in women who were rare fish consumers compared with regular fish eaters.1 Research scientists consistently found a reduced level of omega-3 fatty acids in patients with mood disorders and mental illness. There is overwhelming evidence that omega-3 fatty acids are important to mental health.

The two main omega-3 fatty acids in fish oil, EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid), have important biological functions in the brain. DHA is a major structural component of neuronal membranes, and changing the fatty acid composition of neuronal membranes leads to functional changes in the activity of receptors and other proteins embedded in the membrane phospholipid. EPA has important physiological functions that can affect neuronal activity. Clinical trials have suggested benefits from DHA and EPA treatments in borderline personality disorder, bipolar or manic-depressives, schizophrenia, and attention deficit hyperactivity disorder.

Our bodies have the ability to make these important fats from the short chain omega-3 fats found in leafy greens, walnuts, flax, and hemp, but some people do not fabricate sufficient DHA from the shorter length precursors as well as other people do, predisposing them to neurological problems. These individuals have a greater need to supplement their diets, especially since fish today is so polluted, and farm-raised fish is no longer a dependable source of DHA and EPA. Using a DHA supplement or purified fish oil is cleaner and more dependable.

Documented benefitsThe following interesting observations are found in the scientific literature:
1. Both lower DHA content in mothers’ milk and lower seafood consumption were associated with higher rates of postpartum depression.2

2. Depressed patients have lower levels of DHA in their fatty tissues compared to normals.3

3. Multiple studies indicate that in depression and schizophrenia, one gram a day of the EPA component is more effective than DHA, and a higher dose does not add additional efficacy

4.Depression is related to low levels of these long chain omega-3 fats in the brain, and it is apparent that supplementation with DHA and EPA have beneficial results in patients with mood disorders.

Since studies have shown that EPA is even more effective than DHA for alleviating depression in the short run, and DHA is more important for structural normalcy to maintain long-lasting results, I recommend real fish oil containing both EPA and DHA for those with depression and related mood disorders. About two grams of fish oil usually contains about one gram of active ingredient (EPA + DHA) appropriate for those with mild mood disorders. With major depression, use about 3 grams to achieve the one gram of EPA that has documented clinical efficacy for depression. Look for an oil that gives the most active ingredients (EPA + DHA) per gram of oil.

For more information about these Metagenics products, please call us at: 208-325-9292 or by e-mail at jes@jescollection.com. Web-site: www.jescollection.com or www.jescollection.meta-ehealth.com

No nutrient is more important for decreasing cardiovascular death—and more lacking—than omega-3

Monday, August 11, 2008

From Fish Oil to Medicine
No nutrient is more important for decreasing cardiovascular death—and more lacking—than omega-3
By Bernadine Healy M.D.

With all the talk about fat being bad—whether it's on our bodies or in our diet—we have failed to take seriously a significant nutritional fat deficiency that afflicts most Americans: We have too little omega-3s of the kind found in oily fish, which cannot be made by the human body yet are essential to metabolism. Even though we need only a small dose, our western diet runs woefully low, forcing our cells to run their engines slightly off balance. Over time, this takes its toll. The deficiency significantly increases the risk of heart attacks and sudden cardiac death, and mounting evidence suggests omega-3 shortages contribute to problems as disparate as premature birth, neurological disorders, mental illness, autoimmune disease, obesity, and certain cancers. This is no fish story: Raising omega-3s could be as important to public health as lowering cholesterol.

Think about that comparison. Reining in our nation's cholesterol levels over the past 40 years has yielded great benefit to health and longevity. The change was a grass-roots effort driven by individuals—patients motivated by test results and doctors who helped monitor and manage them. The National Cholesterol Education Program even launched a "know your number" campaign. But who knows their levels of omega-3s?

Well, we should. Omega-3 compounds, eicosapentaenoic acid, or EPA, and docosahexaenoic acid, or DHA, become embedded in the membrane of each of the trillions of cells that make up the body, and from that perch influence cell structure and function, including cell-to-cell communication and electrical stability. On demand, they also generate a reservoir of hormone like molecules to help blood vessels relax, tame inflammation, and reduce blood clotting. All cells feel the pinch of omega-3 deficiencies. Like a car that's out of tune, they run at a suboptimal level and are more prone to breakdown.

Based on what we currently know, says William Harris, director of metabolism and nutrition research at Sanford Research in Sioux Falls, S.D., there is no nutrient more important for decreasing risk of cardiovascular death—and more lacking—than omega-3. And its benefit to other organs is rapidly taking shape.

It is possible to measure a person's omega-3 levels, but the tests are used mainly for research. We don't yet know the range of acceptable values (as was the case for cholesterol), so there is a compelling need to determine optimal levels for age, sex, or medical condition. Knowing one's personal blood levels are too low would motivate dietary change or supplement use, and repeat testing would measure the patient's progress. Though the test is not covered by most insurance, individuals can get their numbers at boutique labs for $100 to $200.

Taking aim. For now, people use dietary targets rather than blood-level goals—that is, if they think about omega-3s at all. The recommendation of several public health organizations that everyone eat fish twice a week just isn't on the radar screens of most homes or doctor's offices. Moreover, not everyone responds the same way to a meal of omega-3s. Genes influence levels of omega-3s in the body, much as they do cholesterol. Some people, such as women of childbearing age, seem to be more effective in generating EPA and DHA from a lesser source, called alpha linolenic acid, found in certain plant oils. And, of course, not every fish meal delivers the same dose of nutrients. Nevertheless, the Japanese, who consume eight to 15 times more fish than we do—and have higher omega-3 blood levels to prove it—experience less heart disease and greater longevity despite smoking more.

Though the medical and nutrition communities generally believe eating fatty fish is the way to go, refined fish oil supplements with specified doses of EPA and DHA can make for a more certain prescription, and one that alleviates concerns about fish being contaminated with mercury or PCBs. (Nasty fish burps can be avoided by freezing the gel capsules and taking them at bedtime. And vegans can find supplements derived from algae, the fishes' omega-3 source.) The FDA, which oversees supplements, advises that patients should not take more than 2 grams without physician guidance. There is now a highly refined prescription form of omega-3 called Lovaza that can deliver the DHA and EPA at levels of 4 grams or more.

That's right. The FDA has approved an omega-3 pill as a medicine. So, we have a treatment and we have a blood test. Before long, your personal omega-3 index just could be the new cholesterol—the number you want to brag about.

Which fish oil do you use? How does it stack up to Metagenics EPA/DHA? Did you know Metagenics EPA/DHA is less expensive gram per gram than most professional brands, and have you seen Metagenics multiple purity assays? Please give us a call to see how your oil stacks up! JES 208-325-9292 www.jescollection.meta-ehealth.com

Natural Treatment for Fibromyalgia

Natural Treatment Protocol for Fibromyalgia

CorvalenM (1 scoop 2X/day in water with food (Take 1 scoop 3X/day for the first 3 weeks) and then decrease to 2X/day). CORvalenM contains pure Bioenergy RIBOSE to help your cells and tissues make the energy they need to stay healthy. It also provides magnesium and malate, vital ingredients your body needs to use energy efficiently. Ribose has been gaining a lot of attention because it has been clinically proven to be critical in rebuilding cellular energy. The result of energy restoration leaves people feeling less pain with more energy. This unique, safe, and clinically proven combination of ingredients accelerates your body's own natural process of energy synthesis and utilization. Ribose is a five-carbon monosaccharide that is vital for the cellular synthesis of ATP (adenosine triphosphate). Adenosine triphosphate is the energy of life and ribose is one of the fundamental building blocks of ATP. Supplemental ribose has been proven to effectively speed energy recovery in cells, represented in improved cardiac function, muscle recovery and overall quality of life.

Metagenics COQ10 ST-100 (1 gel cap 2X/day with meals) Important in energy production, enhances immune function, decrease the frequency of migraine headaches, assist weight loss when dieting, improve exercise tolerance in sedentary people, decrease allergies.

Metagenics EPA/DHA Extra Strength 720 (2 gel caps 2X/day with meal (fat). Fish oil levels are low in CFS/FMS patients. Decrease anger, anxiety, depression, increase vigor, improve attention, cognition, physiological functions and mood. Decreases dry eyes.


Metagenics Myocalm (2 tablets up to 3 tabletsAs needed for muscle tightness). Natural muscle relaxer, tension, anxiety. Supplies important minerals involved in muscular contraction and relaxation responses. May help relieve minor muscle pain associated with stress or physical exertion, and may prevent nocturnal leg muscle cramps.

Metagenics Fibroplex or Fibroplex Plus
Metagenics Fibroplex has: Thiamin (as thiamin mononitrate) 50 mgVitamin B6 (as pyridoxine HCl) 50 mgMagnesium (as magnesium bis-glycinate†) 150 mgManganese (as manganese glycinate†) 5 mgMalic Acid 600 mg. (2-4 tablets 2X/day (pain & energy) Take up to 8 tablets a day to find your correct dose)
Metagenics Fibroplex® Plus - Support for Muscle Tenderness and Discomfort
Fibroplex® Plus provides targeted nutritional support for soft tissues in those with muscle tenderness and discomfort. Featuring a blend of specific vitamins, minerals, and amino acids in an easy-to-use delivery form, this specialized formula works by supporting cellular energy production and muscular and nervous system function.Provides targeted nutrition for soft tissue in those with muscle tenderness and discomfort. Provides targeted support for energy metabolism and neuromuscular function. Supports cellular energy production and mitochondrial function. Provides magnesium in the form of an amino acid chelate designed to be easily absorbed.
In recent years, evidence has accumulated to suggest that FM is the result of local hypoxia in the muscles. For instance, patients with FM have low muscle-tissue oxygen pressure in affected muscles, and to a lesser degree the same was found in other tissues. Muscle biopsies from affected areas showed muscle tissue breakdown and mitochondrial damage. Additionally, low levels of the high energy phosphates ATP, ADP, and phosphocreatine were found. It has been hypothesized that in hypoxic muscle tissues glycolysis is inhibited, reducing ATP synthesis. This stimulates the process of gluconeogenesis, which results in the breakdown of muscle proteins to amino acids that can be utilized as substrates for ATP synthesis. This muscle tissue breakdown, which has been observed in muscle biopsies taken from FM patients, is hypothesized to result in the muscle pain characteristic of FM. Malic acid is both derived from food sources and synthesized in the body through the citric acid (Krebs) cycle. Its importance to the production of energy in the body during both aerobic and anaerobic conditions is well established. Under aerobic conditions, the oxidation of malate to oxaloacetate provides reducing equivalents to the mitochondria through the malate-aspartate redox shuttle. During anaerobic conditions, where a buildup of excess of reducing equivalents inhibits glycolysis, malic acids simultaneous reduction to succinate and oxidation to oxaloacetate is capable of removing the accumulating reducing equivalents. This allows malic acid to reverse hypoxias inhibition of glycolysis and energy production. This may allow malic acid to improve energy production in FM, reversing the negative effect of the relative hypoxia that has been found in these patients.Because of its obvious relationship to energy depletion during exercise, malic acid may be of benefit to healthy individuals interested in maximizing their energy production, as well as those with FM. In the rat it has been found that only tissue malate is depleted following exhaustive physical activity. Other key metabolites from the citric acid cycle needed for energy production were found to be unchanged. Because of this, a deficiency of malic acid has been hypothesized to be a major cause of physical exhaustion. The administration of malic acid to rats has been shown to elevate mitochondrial malate and increase mitochondrial respiration and energy production. Surprisingly, relatively small amounts of exogenous malic acid were required to increase mitochondrial energy production and ATP formation. Under hypoxic conditions there is an increased demand and utilization of malic acid, and this demand is normally met by increasing the synthesis of malic acid through gluconeogenesis and muscle proteinbreakdown. This ultimately results in muscle breakdown and damage.In a study on the effect of the oral administration of malic acid to rats, a significant increase in anaerobic endurance was found. Interestingly, the improvement in endurance was not accompanied by an increase in carbohydrate and oxygen utilization, suggesting that malic acid has carbohydrate and oxygen-sparing effects. In addition, malic acid is the only metabolite of the citric acid cycle positively correlated with physical activity. It has also been demonstrated that exercise-induced mitochondrial respiration is associated with an accumulation of malic acid. In humans, endurance training is associated with a significant increase in the enzymes involved with malic acid metabolism.Because of the compelling evidence that malic acid plays a central role in energy production, especially during hypoxic conditions, malic acid supplements have been examined for their effects on FM. Subjective improvement in pain was observed within 48 hours of supplementation with 1200 - 2400 milligrams of malic acid, and this improvement was lost following the discontinuation of malic acid for 48 hours. These studies also used magnesium supplements, due to the fact that magnesium is often low in FM patients. Therefore, malic acid supplements may be of benefit in these conditions. Chronic Fatigue Syndrome has also been found to be associated with FM, and malic acid supplementation may be of use in improving energy production in this condition as well. Lastly, malic acid may be of use as a general supplement aimed at ensuring an optimal level of malic acid within the cells, and thus, maintaining an optimal level of energy production.

Metagenics MyocalmPM (3 tablets 60 minutes before bedtime) Useful as a sleep aid, muscle and tension relief. Promotes a feeling of calm.

Metagenics Tran-Q (relax muscles, ease tension) 6-8 tablets/day in divided doses if muscles still tense/tight with Myocalm. Helps to promote relaxation and sense of well being.

Metagenics UltraInflamX
See UltraInflamXModified Step Program for directions. May lower inflammatory response by modulating the pro-inflammatory “cascade”, supporting the anti-inflammatory “pathways”, and quenching the excessive free-radical production that may be associated with increased inflammation. Important in all chronic inflammatory conditions. Useful in fibromyalgia.

Depression & Anxiety Natural Relief

There is clinical proof that symptoms of depression and anxiety can be relieved in many patients who supplement with certain vitamins, minerals, and herbal preparations, including:
Omega-3 fatty acids
Vitamin D
B vitamins (especially B-12 and folate)
Magnesium
St. John's wort
Valerian root

Talk to your doctor before adding any of these supplements to your daily regimen.

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Also, very important is the quality/brand of the supplements you take. Don't buy brands made in China. Don't buy your supplements at places like Wal-Mart, Costco, etc. Look for high quality supplements like Metagenics in glass bottles. There is also some evidence that Omega-3 fatty acids help to decrease or manage anger.