Wellness Review
Fibromyalgia
Report 1A - Revision 1 - March 21, 2003

Jeff Gold, Senior Scientist, Advanced Research Programs
World Environmental Organization; Ph: (706) 769-1000; Email: JGold@World.Org


Discussion

A review of nonpharmacological therapies for fibromyalgia (FM) has revealed that mind-body therapies (such as nutrition, exercise, massage, etc.) are much more effective than conventional drug treatments for this set of disorders. This article will present information gathered from research into these areas.

The findings of several studies suggest that FM patients receive maximum therapeutic benefit from a program of moderate to intensive aerobic exercise combined with a high fiber diet consisting largely of fruits, vegetables and grains, and modest nutritional supplementation.

When taken as a whole, the findings of some studies point to the hypothesis that a potential new treatment for FM could be supplementation with a combination of folate (folic acid), vitamin B12, vitamin B6 and riboflavin (vitamin B2).

Numerous studies have demonstrated that this combination of B vitamins substantially reduces total homocysteine (tHcy) levels in the body.(1-11) Most tHcy studies have been done in recent years because lowering tHcy levels has been found to help patients with coronary artery disease.(1,2,12,13) A vascular disease meta-analysis suggests that prolonged lowering of tHcy concentrations could save tens of thousands of lives each year.(14) The lowering of tHcy levels may also be relevant to FM patients (and potentially to Chronic Fatigue Syndrome patients) based on the findings of a 1996 study conducted at Uddevalla Hospital in Sweden.(15)

The Swedish study found that of the 12 patients with symptoms of both FM and Chronic Fatigue Syndrome studied, all 12 (100%) of them had unusually high levels of tHcy in their cerebrospinal fluid. While this study was of a small sample, the 100% rate of elevated tHcy makes it probable that a larger study would have similar findings.

Another noteworthy finding from the Swedish study was that each patient’s level of tHcy was positively correlated with their level of fatigability. By combining the findings of the Swedish study with those of other tHcy studies, one could hypothesize that decreasing tHcy through B vitamin supplementation may benefit FM patients.

Another finding of the Swedish study was that of the 12 patients studied, 10 of them (83%) had abnormally low levels of vitamin B12 in their cerebrospinal fluid. Only two had vitamin B12 levels within the normal range. This finding further supports a hypothetical treatment for FM that includes vitamin B12 supplementation.

Several studies have found that many patients with depressive disorders have elevated tHcy levels. B vitamins may, therefore, also be relevant in treating depression, a frequent symptom of FM patients. It is also interesting to note that serum folate levels have been found to be low in as many as 70% of patients with rheumatoid arthritis(16), another condition that could possibly be treated with vitamin supplementation.

While there has yet to be a direct study to determine the therapeutic value of B vitamins for FM, there is no reason not to try this now, particularly since B vitamins have few if any known adverse effects(3), and many benefits. Most studies point to a 25-31% lowering of tHcy1 within four weeks of the start of B vitamin therapy.(4,5,12) Any positive results would, therefore, likely occur in FM patients within the first months of vitamin therapy.

In additional to the potential benefit to FM patients, B vitamins have been studied recently for treating a variety of disorders including coronary disease(1,2,12,13), Alzheimer disease(3) and for lowering tHcy in patients receiving hemodialysis(6) and those on antiepileptic drugs(5).

The alteration of diet to increase the intake of foods containing natural B vitamins could also benefit FM patients. Several foods have been found to lower tHcy levels including pulses (chickpeas, beans, peas and lentils), green leafy vegetables, fruits, cereals, egg yolks, liver and nuts.(4,13) A diet that is rich in natural folate also offers additional benefits because of its lower content of saturated fatty acids and higher content of various vitamins and minerals.(4)

People wanting to lower tHcy should be advised to avoid things that elevate tHcy including high coffee or alcohol consumption, smoking and lack of physical activity.(13)

It would be helpful to conduct a placebo-controlled study using B vitamins to determine their actual usefulness for FM and to see if the hypothesis presented here is true. It would also be useful to conduct a study with a large number of subjects with FM to determine the statistical occurrence of elevated tHcy and lowered vitamin B12 levels.

It has been found that the most important of the B vitamins is folate(4,6,7), however, since the remethylation of tHcy to methionine in the body also requires vitamin B12 and riboflavin, it is important for the body to be replete with all of these. Vitamin B6 has also been found to enhance the effect of folate supplementation.(1,8)

The therapeutic value of various B vitamin doses has been tested in numerous studies and a meta-analysis of these randomized trials found an effective and safe daily combination to be 0.5 mg of folic acid with 1 mg of vitamin B12. Large (10 mg) and small (0.5 mg) doses of folic acid were found equally effective, however, the meta-analysis went on to state that higher doses may be of benefit to people at high risk.(1) A cardiovascular study compared the effect of 2.5 mg versus 10 mg daily of folic acid and found no statistical difference between the two groups.(12) The exact dosages of Vitamin B6 and riboflavin do not seem to be as crucial. One trial that included vitamin B6 used a daily dose of 50 mg.(3) Riboflavin was used at a daily dose of 1.6 mg in a different trial.(8)

At high doses (5 mg or more per day), folic acid can mask the hematologic manifestation of unrecognized pernicious anemia.(14) Since there is no apparent benefit of such high doses, this situation can be avoided simply by keeping daily doses well under 5 mg.

Supporting the hypothesis of possible treatment of FM with B vitamins is a study that found FM patients show remarkable improvement when they consume nutritional supplements of their own choosing.(17) Since B vitamins are contained in most standard multivitamin supplements, it is possible these were the source of benefit to FM patients.

Also related to nutrition, a study in Finland demonstrated benefit from an uncooked vegan diet. After changing to such a diet, FM patients experienced a substantial decrease in join stiffness and pain as well as an overall improvement of their self-experienced health. After switching back to their original omnivorous diets, symptoms worsened.(18)

It was theorized in the study that improvements from the vegan diet result from increased antioxidants in the blood and affected tissues, diminishing the actions of radicals. The Finnish research concluded that the vegan diet is effective based upon its microbiologic effects, not its subjective and mental effects as others had previously theorized. It is possible that the enhanced presence of folate, vitamin B6 and riboflavin in a vegan diet may have been a contributing factor if the hypothesis proposed earlier proves to be correct.

It should be noted that vitamin B12 is only derived from animal sources and, accordingly, is not present at all in a vegan diet.(13) Patients who follow vegan or vegetarian diets should, therefore, be monitored to ensure that they receive adequate amounts of vitamin B12, as well as vitamin D and calcium.(18) Foods rich in these substances and/or appropriate supplements should be incorporated into the diet.

Also found to support the use of nutritional therapies for FM was a study conducted at the Medical College of Virginia. This FM study compared the effects of supplementation with chlorella (a fresh water alga) with a placebo. Pain was reduced in a statistically significant fashion in the group taking chlorella. Further, it was found that chlorella may reduce high blood pressure, lower serum cholesterol levels, accelerate wound healing and enhance immune functions. Several studies have suggested that FM is associated with growth hormone deficiencies. Levels of insulin-like growth factor I are also frequently reduced in FM patients. It has been theorized that chlorella consumption might increase production of growth hormone, and perhaps this contributes to its lessening of symptoms from FM.(19)

An extensive review of nonpharmacological interventions for FM conducted by researchers in the United Kingdom found the most noteworthy intervention of those reviewed to be aerobic exercise, which provided significant benefit in three studies.(20)

Additional research finds that therapies such as biofeedback, hypnosis and cognitive behavioral therapy provide modest relief of symptoms in some cases.(21) These therapies, however, do not seem nearly as effective as regular exercise and proper nutrition.

Acupuncture is sometimes used to treat FM patients; however, it should be used with caution as acupuncture has been found to exacerbate symptoms in some FM patients. A recent NIH conference concluded similarly that acupuncture is effective for acute pain but there is little evidence that it helps with chronic pain syndromes such as FM.(21)

Doctors from the Complementary Medicine Program at the University of Maryland conducted an extensive study of thirteen mind-body trials involving 802 FM patients. The results of this study were largely inconclusive except for the study’s confirmation that moderate to high intensity exercise provides considerable benefit to FM patients.(22)

It is important to note that this same study found that many FM patients have difficulty mastering mind-body interventions.(22) It, therefore, may be better for caregivers to find ways to help patients actually eliminate contributing unhealthy and stress-inducing lifestyle factors rather than simply trying to teach coping strategies.

In contrast to mind-body therapies, conventional medical treatments have provided little help to FM patients. One long term placebo-controlled study, and several other studies, have demonstrated that conventional pharmacological treatments for FM such as amitriptyline and cyclobenzaprine offer no long term benefits to patients, with only brief initial improvement in 25% of patients.(23) This evidence combined with the potential for side effects from such medicines negates recommending such a course of treatment.

In the face of these findings, it should be noted that there has been considerable debate as to whether or not FM is a distinct clinical disease. Current evidence points to FM being a disorder characterized by a set of common symptoms, rather than a clinical disease.(17) FM is perhaps best considered within a biopsychosocial model of pain.(22) This is further confirmed by a study of 60 FM patients published in the Journal of the American Academy of Nurse Practitioners. The study found that half of the most successful treatments reported by FM patients were psychological or social in nature, with some of the best therapies found to include support groups, writing, diversion and social contact.(24)

The same study also reported FM patients achieve significant success with several complementary therapies including aromatherapy, heat and massage, each of which provided relief to more than 80% of the patients surveyed. This study also confirmed frequent failures with acupuncture, which was found effective by only 29% of those surveyed.(24)

Despite its unclear classification, the symptoms of FM are consistent across large groups of people with the disorder. An accurate assessment of current therapies is, therefore, essential to providing each patient with the best care possible.


Proposed Treatment Protocol Based Upon Current Research

1. Folic Acid (2.4 mg/day), Vitamin B12 (1 mg/day), Vitamin B6 (50 mg/day) and Riboflavin (1.6 mg/day).

2. Increased intake of foods rich in folate and B vitamins such as green leafy vegetables, chickpeas, beans, peas, lentils, fruits, cereals, egg yolks, liver and nuts.

3. Elimination or reduction of coffee consumption, smoking and alcohol consumption.

4. Chlorella supplementation.

5. Frequent moderate to intensive aerobic exercise.

6. Mind-Body therapies that focus on changing life circumstances to decrease stress and increase healthy interpersonal relationships.

7. Addition of a general multivitamin and mineral supplement to the diet.

8. Aromatherapy.

9. Heat.

10. Massage.

11. Stretching.

12. Increased social contact.


References

1. Clarke R, Homocysteine Lowering Trialists' Collaboration. Lowering blood homocysteine with folic acid based supplements: meta-analysis of randomised trials. BMJ 1998 Mar 21;316(7135):894-8. ABSTRACT ARTICLE

2. O'Connor JJ, Meurer LN. Should patients with coronary disease and high homocysteine take folic acid? J Fam Pract 2003 Jan;52(1):16-8.

3. Aisen PS, Egelko S, Andrews H, Diaz-Arrastia R, Weiner M, DeCarli C, Jagust W, Miller JW, Green R, Bell K, Sano M. A pilot study of vitamins to lower plasma homocysteine levels in Alzheimer disease. Am J Geriatr Psychiatry 2003 Mar-Apr;11(2):246-9.

4. Venn BJ, Mann JI, Williams SM, Riddell LJ, Chisholm A, Harper MJ, Aitken W. Dietary counseling to increase natural folate intake: a randomized, placebo-controlled trial in free-living subjects to assess effects on serum folate and plasma total homocysteine. Am J Clin Nutr 2002 Oct;76(4):758-65.

5. Apeland T, Mansoor MA, Pentieva K, McNulty H, Seljeflot I, Strandjord RE. The effect of B-vitamins on hyperhomocysteinemia in patients on antiepileptic drugs. Epilepsy Res 2002 Oct;51(3):237-47.

6. Ziakka S, Rammos G, Kountouris S, Doulgerakis C, Karakasis P, Kourvelou C, Papagalanis N. The effect of vitamin B6 and folate supplements on plasma homocysteine and serum lipids levels in patients on regular hemodialysis. Int Urol Nephrol 2001;33(3):559-62.

7. Narin F, Narin N, Akcakus M, Ustdal M, Karakucuk I, Halici C. The effect of folic acid, vitamin B6 and vitamin B12 on the homocysteine levels in rabbits fed by methionine-enriched diets. Tohoku J Exp Med 2002 Oct;198(2):99-105.

8. McKinley MC, McNulty H, McPartlin J, Strain JJ, Pentieva K, Ward M, Weir DG, Scott JM. Low-dose vitamin B-6 effectively lowers fasting plasma homocysteine in healthy elderly persons who are folate and riboflavin replete. Am J Clin Nutr 2001 Apr;73(4):759-64.

9. Bartels PC, Schoorl M, Peetoom JJ. Effect of nutrient supplementation on serum homocysteine, iron and proteins in psychogeriatric patients. Clin Lab 2003;49(1-2):29-34.

10. Cafolla A, Dragoni F, Girelli G, Tosti ME, Costante A, De Luca AM, Funaro D, Scott CS. Effect of folic acid and vitamin C supplementation on folate status and homocysteine level: a randomised controlled trial in Italian smoker-blood donors. Atherosclerosis 2002 Jul;163(1):105-11.

11. Shimakawa T, Nieto FJ, Malinow MR, Chambless LE, Schreiner PJ, Szklo M. Vitamin intake: a possible determinant of plasma homocyst(e)ine among middle-aged adults. Ann Epidemiol 1997 May;7(4):285-93.

12. Landgren F, Israelsson B, Lindgren A, Hultberg B, Andersson A, Brattstrom L. Plasma homocysteine in acute myocardial infarction: homocysteine-lowering effect of folic acid. J Intern Med 1995 Apr;237(4):381-8.

13. Krishnaswamy K, Lakshmi AV. Role of nutritional supplementation in reducing the levels of homocysteine. J Assoc Physicians India 2002 May;50 Suppl:36-42.

14. Boushey CJ, Beresford SA, Omenn GS, Motulsky AG. A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. Probable benefits of increasing folic acid intakes. JAMA 1995 Oct 4;274(13):1049-57.

15. Regland B, Andersson M, Abrahamsson L, Bagby J, Dyrehag LE, Gottfries CG. Increased concentrations of homocysteine in the cerebrospinal fluid in patients with fibromyalgia and chronic fatigue syndrome. Scand J Rheumatol 1997;26(4):301-7.

16. Varela-Moreiras G. Nutritional regulation of homocysteine: effects of drugs. Biomed Pharmacother 2001 Oct;55(8):448-53.

17. Dykman KD, Tone C, Ford C, Dykman RA. The effects of nutritional supplements on the symptoms of fibromyalgia and chronic fatigue syndrome. Integr Physiol Behav Sci 1998 Jan-Mar;33(1):61-71.

18. Hanninen, Kaartinen K, Rauma AL, Nenonen M, Torronen R, Hakkinen AS, Adlercreutz H, Laakso J. Antioxidants in vegan diet and rheumatic disorders. Toxicology 2000 Nov 30;155(1-3):45-53.

19. Merchant RE, Andre CA. A review of recent clinical trials of the nutritional supplement Chlorella pyrenoidosa in the treatment of fibromyalgia, hypertension, and ulcerative colitis. Altern Ther Health Med 2001 May-Jun;7(3):79-91.

20. Sim J, Adams N. Systematic review of randomized controlled trials of nonpharmacological interventions for fibromyalgia. Clin J Pain 2002 Sep-Oct;18(5):324-36.

21. Berman BM, Swyers JP. Complementary medicine treatments for fibromyalgia syndrome. Baillieres Best Pract Res Clin Rheumatol 1999 Sep;13(3):487-92.

22. Hadhazy VA, Ezzo J, Creamer P, Berman BM. Mind-body therapies for the treatment of fibromyalgia. A systematic review. J Rheumatol 2000 Dec;27(12):2911-8.

23. Carette S, Bell MJ, Reynolds WJ, Haraoui B, McCain GA, Bykerk VP, Edworthy SM, Baron M, Koehler BE, Fam AG, et al. Comparison of amitriptyline, cyclobenzaprine, and placebo in the treatment of fibromyalgia. A randomized, double-blind clinical trial. Arthritis Rheum 1994 Jan;37(1):32-40.

24. Barbour C. Use of complementary and alternative treatments by individuals with fibromyalgia syndrome. J Am Acad Nurse Pract 2000 Aug;12(8):311-6.




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