Guaifenesin and A Hypoglycemic Diet in Fibromyalgia By J.C. Waterhouse, Ph.D. Part D. The Oregon Guaifenesin Study: Responses to Misconceptions A number of misunderstandings have arisen regarding Dr. R. Paul St. Amand's use of guaifenesin for fibromyalgia and the study done by Dr. Robert Bennett on guaifenesin in 1995 at the Oregon Health Sciences University (Thorsen, 1998). Dr. Bennett concluded, based on this double blind, placebo controlled study, that guaifenesin was no better than a placebo. Dr. St. Amand is convinced that several major flaws in the study caused this failure to show guaifenesin’s effectiveness (St. Amand and Malek, 1997 and 1999; St. Amand 1998). It is hoped that the following point by point discussion will help clear up the misconceptions. Part of the problem seems to arise from Dr. St. Amand's inclusion of a historical account of how he came to believe uricosuric drugs could be helpful in fibromyalgia. In this historical account, certain observations are made that illustrate the process of his discovery, but are not really directly relevant to his current theory to explain the success of these drugs based on over 30 years of experience in successfully treating fibromyalgia patients. 1. Misconception: It has been said that Dr. St. Amand says that large crystalline calcium phosphate deposits in muscles are the cause of fibromyalgia. Since researchers do not generally find these crystals, then Dr. St. Amand's theory must be wrong. Response: It is excess calcium and phosphate inside cells that Dr. St. Amand theorizes are the cause of fibromyalgia. The misunderstanding arose because Dr. St. Amand began his account by describing how a patient found that when using uricosuric medication for gout, the patient was able to scrape tartar (composed of calcium and phosphate) from his teeth with his fingernail. This observation was the clue that led Dr. St. Amand to try uricosuric drugs on fibromyalgia patients. He reasoned that there might be a similarity between calcium phosphate deposits, and some process occurring in tender areas related to excess calcium and phosphate in the saliva and serum. This phenomenon of the tartar effect is not found regularly in his FMS patients; it was simply the clue that led him to initiate his trial of uricosuric drugs in FMS. His later experience and study led him to conclude that most of the calcium and phosphate storage in tender areas was due to excess phosphate (due to inadequate kidney excretion) entering the cell and being followed by calcium to balance the charge. This excess intracellular calcium and phosphate results in lowered ATP and continual cell contraction, occurring by well-known biochemical processes. Both the lowered ATP and the muscle contractions have been observed in FMS. It may be that in some unusual cases crystals may be found as well. Calcium phosphate crystals in joints are also a well-known feature of osteoarthritis. Dr. St. Amand thinks there is a close connection between FMS and osteoarthritis based on his observation of the pattern of illness within families he has observed. However, calcium phosphate in the form of crystals in muscle tissue in FMS appear to be the exception and not the rule, thus explaining why many researchers have not observed them. The excess calcium and phosphate are primarily inside the cells where they cause lowered ATP and continual muscle contraction. 2. Misconception: Salicylates were eliminated in the study, so the treatment should have worked. If there were hidden sources of salicylates that Dr. St. Amand only recently discovered, then how was the treatment working all this time for Dr. St. Amand. Response: Not all sources of salicylates were eliminated in the study because many were not known about until the study was over. There was a great increase in the use of salicylates in cosmetics, lotions and other products around the time of the study. One reason is that the public's recent concern about skin cancer has led products to add sunscreen protection to all sorts of products. Previously UVA protection was added to some things, but recent addition of a UVB protectant, almost always a salicylate, has greatly increased. Also, the addition of herbal extracts, like aloe, has become very common. One now has to make a special effort to find products without salicylates. Speculations by dermatologists as to how much cosmetic would be needed to provide an amount of salicylate able to block the treatment would not be likely to be reliable since they would be unlikely to have any firsthand experience of the use of guaifenisen in treating FMS. There is no question that absorption of many compounds through the skin is often more effective than when taken orally and this effect is being used with a number of drugs, including aspirin (salicylic acid). Of course, there is clearly much that is not known. Even Dr. St. Amand does not know why some people are more sensitive to the effects of salicylates than others. In some cases, where there may have been some hidden salicylates in Dr. St. Amand's patients, it appears that dosage increases were enough to overcome it. In some patients he has had to use as many as 3 or 4, or even as many as 6 or 8 guaifenisen tablets per day. The study, however, used a uniform two pills per day (1200 mg) which generally is enough for only 70% of Dr. St. Amand's patients, even when salicylates are avoided. So with unknown amounts of hidden salicylates, the percentage of response would be considerably lower. 3. Misconception: Since phosphate excretion was not observed in the study, then Dr. St. Amand's theory is wrong. Response: Since the guaifenisen effect was apparently blocked in most patients, then one would not expect changes in phosphate excretion in any case. However, even if the guaifenisen had not been blocked, Dr. St. Amand finds that phosphates in the urine are quite variable because their excretion depends on so many factors, like diet and deposition in bone and teeth (where most phosphate in the body is found), and the cycles of the guaifenesin reversal process. Dr. St. Amand did observe, however a 60% increase in phosphate excretion, and a smaller increase in calcium and oxalate in the urine in a small study using one of the uricosuric drugs he had used previously, when he carefully had the patients keep their diet constant (St. Amand, 1998). That was one of the reasons he originally theorized that phosphate excretion was the key to why the uricosuric drugs worked in fibromyalgia. 4. Misconception: Cycling of symptoms was not found in the study, thus Dr. St. Amand's theory must be wrong. Changes in tender points did not indicate that guaifenisen was effective either. Response: Since the guaifenisen was apparently blocked, the cycling and changes in tender areas would not be expected. 5. Misconception: Uric acid level changes in the urine or blood should have revealed whether patients were getting any hidden salicylates. These changes were not observed, and therefore the patients were not exposed to any salicylates. Response: Since Dr. St. Amand believes that the effect of guaifenisen has no relationship to uric acid, then this is not relevant to the action of guaifenesin in enhancing phosphate excretion. The uricosuric effect (i.e., causing an increase in uric acid in the urine) was only relevant in that it led him to focus on a process occurring at the level of the kidney. In other words, the uricosuric effect was just a clue pointing to a kidney level process being involved in FMS. Clearly, if urates had a direct relevance to fibromyalgia, then the more strongly uricosuric drugs he had used previously would have worked better on fibromyalgia than guaifenisen, which is only weakly uricosuric. Dr. St. Amand and his patients have witnessed the rapid reversal of progress that has been clearly traced to changing to a brand of cosmetics that has added salicylates. This apparently occurs because guaifenisen is affected by salicylates in a way that is analogous to the way salicylates affect uricosuric gout medication. This is because they apparently both involve somewhat similar renal excretion mechanisms with one affecting mainly urates and the other affecting primarily phosphates. 6. Misconception: The placebo effect accounts for the recovery of Dr. St. Amand's patients and occurred in the study as well. Response: The placebo effect generally only occurs for about 3 months and then patients typically return to their previous state or worse. Dr. St. Amand's patients and many other patients who go to different doctors that use guaifenesin for fibromyalgia (Dr. St. Amand has a list of over 130 doctors who have used it) continue to improve over the long term and regain greater health than patients using conventional treatment, to the point where they are eventually symptom-free. I have postulated that one explanation for the mild improvement in both treatment and control groups reported in the Oregon study may relate to hypoglycemia, another important component in about half of Dr. St. Amand's patients. I wonder how many of the study subjects in both the treatment and control groups had read Dr. St. Amand's paper and had cut back partially on sugar and other concentrated carbohydrates during the study period. This might possibly have resulted in the mild improvement in both study and control groups on average. I know I would have had a tendency to cut back on glycemic foods if I had hypoglycemia and were in the study (perhaps even subconsciously), if I were aware of the dietary recommendations. 7. Misconception: One must go through excruciating pain for a long time with guaifenesin, and patients will be forsaking other more beneficial treatments. Response: First of all, one does not need to give up any other treatment methods, unless they involve herbs. Other pain medications can be substituted for aspirin and are probably safer for long-term use in any case. Some treatments, like cortisone injections, even become more feasible, since one will not need to continue them indefinitely as guaifenisen leads to improvement. The initial exacerbation of symptoms is primarily during the first few months after an effective dose is achieved and is generally tolerable, especially if one is prepared for it. It was helpful to me to have taken magnesium glycinate and taurine and to have had my food sensitivities treated before starting guaifenesin. Many hypoglycemics and those who crave carbohydrates find that going on the low carbohydrate diet before or during guaifenesin treatment is also very helpful. Guaifenesin may not be an instantaneous cure, but most people find that the initial exacerbation in the first few months is really not that bad, especially when you know it is the process of healing. The lesions took a long time to develop and thus take some time to reverse. Despite my own and many other’s positive experiences with guaifenesin (Waterhouse, 1998, ref. # 23), I agree that further research will be needed to prove the effectiveness of guaifenesin to the medical community. In the meantime, Dr. St. Amand has been and will continue to assist any physician who contacts him. He feels he has a moral obligation to try to educate others so that they will be freed from this trap of pain, which he and his family suffered from at one time, and provides information free of charge to those who request it (send an SASE with 2 stamps to him with your request: 4560 Admiralty Way, Suite 355, Marina Del Rey, CA 90292). Dr. St. Amand takes responsibility for the shortcomings in the Oregon study, for which he was technical advisor. Since he was the only person experienced with this treatment involved in the study, it seems fair to expect that his point of view on the study results should be given precedence. The study should be regarded as a "pilot" study in which valuable lessons can be learned. Another study should be done in which a higher dose should be used, the hypoglycemics should be either removed or treated beforehand with the low carbohydrate diet, and the increased knowledge of hidden salicylates should be utilized. Dr. St. Amand should personally do the tender area mapping on patients, without knowing who is receiving guaifenisen and who is in the control group. Younger patients should be used because they will respond more quickly to treatment and thus it will be easier to see the effects of guaifenesin in a one year study (Editor’s Note: I have been informed that a study along these lines is now in the planning stages).