Vitamin B12 and Fibromyalgia

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Vitamin B12 is a water-soluble vitamin, which means our bodies cannot store it. It therefore must be consumed every day in order to maintain adequate levels. Vitamin B12 is found naturally in some foods, is added to others, and can also be consumed as a dietary supplement or in a prescription-strength formulation. Food sources of vitamin B12 include animal products such as fish, poultry, meat, eggs, milk, and milk products. Clams, liver, trout, salmon, and tuna are among the most abundant natural sources of vitamin B12. Plant foods are not usually good sources of vitamin B12, however fortified breakfast cereals are a good source of vitamin B12 and are therefore a good option for vegetarians. The current Recommended Dietary Allowance (RDA) for vitamin B12 is 2.4mcg (micrograms) for both males and females over the age of 14.

Vitamin B12 plays a vital role in the formation of red blood cells, nervous system functioning, and the production of DNA, RNA, certain hormones, proteins, and fats. Vitamin B12 deficiency most often results from a condition known as pernicious anemia. Individuals with pernicious anemia lack what is known as intrinsic factor, which is a protein that is produced in the stomach and facilitates the absorption of vitamin B12.  Other causes of vitamin B12 deficiency include certain infections, surgery, medication side effects, and diet. Individual vitamin B12 status can be determined by obtaining blood or plasma vitamin B12 levels. In adults, any value below 170-250 pg/mL (picograms per milliliter) is considered indicative of vitamin B12 deficiency.

Most individuals in the United States are able to consume adequate quantities of vitamin B12 on a daily basis through diet. However, some individuals, including those who are older, those with pernicious anemia, and those who have certain intestinal disorders, have difficulty absorbing vitamin B12 from both food and even dietary supplements. Because of this, vitamin B12 deficiency is relatively common and affects anywhere from between 1.5% to 15% of the population, and in many cases, the causes of deficiency are not known.

Symptoms associated with vitamin B12 deficiency include anemia, fatigue, weakness, constipation, decreased appetite, and weight loss. In addition, neurological symptoms may also be present and include numbness and tingling of the hands and feet. Some individuals may experience problems with balance, depression, confusion, dementia and/or memory loss, and sore mouth or tongue. Vitamin B12 deficiency is generally treated with injections of the vitamin, although high doses of oral preparations may also be effective. It is important to note that large amounts of another B-vitamin, commonly known as folic acid or folate, can mask certain side effects of vitamin B12 deficiency, including potentially irreversible neurological damage. In addition, some research suggests that excess blood levels of folic acid may also worsen vitamin B12-deficiency anemia and exacerbate its associated cognitive symptoms. As a result, it is generally recommended that individuals not exceed more than 1,000mcg per day of folic acid (Clarke, 2008; IOM, 1998; Johnson, 2007).

No adverse effects have been associated with excess consumption of vitamin B12, and research findings continue to support this. However, vitamin B12 may have the potential to interact negatively with certain medications. These include the antibiotic medication chloramphenicol, proton pump inhibitors such as omeprazole (Prilosec®) and lansoprazole (Prevacid®), cimetidine (Tagamet®), famotidine (Pepcid®), and ranitidine (Zantac®). In addition, metformin, a common diabetes medication, may reduce the ability of the body to absorb vitamin B12.

Vitamin B12 and Fibromyalgia

The scientific literature regarding a direct association between vitamin B12 and fibromyalgia is extremely limited. A 2010 study investigated the association between blood levels of ferritin, which is a protein that stores iron in the body, and fibromyalgia. Iron is an essential component in the production of various neurotransmitters, several of which have been reported to be found in decreased concentration among fibromyalgia patients (Abeles, 2007; Russell et al., 1992; Legangneux et al., 2001). Of the 46 fibromyalgia patients and 46 healthy female controls studied for the purposes of the investigation, the authors found that a low ferritin level (defined as less than 50ng/mL [nanograms per milliliter]) resulted in a 6.5-fold increase in risk for fibromyalgia. During the course of their analyses, the authors also measured the vitamin B12 levels of each participant, and no differences were found between those in the fibromyalgia group and those in the control group (Ortancil et al., 2010).

The use of intravenous (IV) vitamins and minerals as treatment for certain medical conditions was pioneered by a Baltimore physician named John Myers, M.D.. His therapeutic use of IV vitamins and minerals became known as the “Myers’ cocktail,” however its exact formulation was never fully described by Dr. Myers. Based in part on information provided from former patients of Dr. Myers who sought out similar therapy following his death in 1984, a physician by the name of Alan R. Gaby was able to recreate a similar cocktail, consisting of magnesium chloride, calcium gluconate, thiamine, vitamins B6 and B12, calcium pantothenate, vitamin B complex, vitamin C, and dilute hydrochloric acid. Dr. Gaby began to treat former patients of Dr. Myers using this injectable “cocktail”, and self-reported that it was useful in treating a variety of clinical conditions, including asthma, migraines, chronic fatigue syndrome, fibromyalgia, muscle spasm, upper respiratory tract infections, chronic sinusitis, and allergic rhinitis. Dr. Gaby clams to have treated nearly 1,000 such patients, administering approximately 15,000 injections in total over an 11 year period. In a 2002 paper in which he presents his clinical and theoretical evidence as to why such a cocktail is effective, Dr. Gaby describes the case report of a 48 year old female fibromyalgia patient who was given initial therapy with vitamin C, magnesium, calcium, and vitamins B12, B6, B5, and B complex. The patient reported complete relief from pain immediately following the injection and continued with weekly and monthly treatments for the following three years, in addition to other therapeutic interventions. In his discussion, Dr. Gaby described how he also treated 30 additional fibromyalgia patients with the same regimen. He reported that half experienced significant improvement in their symptoms, most after only three or four injections. Dr. Gaby also reports having successfully treated other patients with symptoms commonly experienced in fibromyalgia, including depression and fatigue (Gaby, 2002). In his discussion, he points to the potential role of vitamin B12 as having an active role in patient improvement for both conditions, and cites rather dated research that supports the use of vitamin B12 as effective therapy for fatigue (Ellis & Nasser, 1973).

Finally, a small study published in 1997 looked at a number of factors, both laboratory and psychological, among twelve females who fulfilled the then-current criteria for a diagnosis of fibromyalgia as well as chronic fatigue syndrome. In their analysis, the authors found that the patients had uniformly high levels of homocysteine (an amino acid) in their spinal fluid, and that these high levels of homocysteine were related to increased fatigue. Furthermore, the authors also found that low spinal fluid levels of vitamin B12 were also significantly related to fatigue. The authors state that such a findings is clinically significant, and point to the fact that vitamin B12 deficiency may be the cause of the increased homocysteine levels found in the patients’ spinal fluid (Regland et al., 1997).

Vitamin B12 and Fibromyalgia Symptoms

Vitamin B12 has been extensively researched to determine its relationship to depression, which is a common symptom for many fibromyalgia patients. A majority of studies have repeatedly found an association between low vitamin B12 and depression (Coppen & Bolander-Gouaille, 2005; Tiemeier et al., 2002), while some have not (Sachdev et al., 2005). Nevertheless, considerable scientific research continues with regard to this association, and many recent studies have begun to suggest that both folic acid and vitamin B12 supplementation may be important additions to conventional therapy for depression (Coppen & Bolander-Gouaille, 2005; Ford et al., 2008; Bottiglieri et al., 2000; Tiemeier et al., 2002).

In addition to depression, vitamin B12 has also been investigated with regard to its association with cognition, and findings may be of interest to fibromyalgia patients who frequently suffer from cognitive difficulties, or “fibro fog.” A 2011 study by Tangney and colleagues found that concentrations of vitamin B12-related markers, though not blood levels of vitamin B12, were associated with overall cognitive functioning among 121 participants, and results suggest that vitamin B12 may have numerous effects on the brain from both structural and functional perspectives (Tangney et al., 2011). Further research has shown that vitamin B12 deficiency may be related to declining cognition in individuals over the age of 60 (McCracken, 2010). Other studies also lend support for an association between low vitamin B12 and folic acid levels and cognition (Moretti et al., 2004; Malouf & Areosa Sastre, 2003).

Supplementation with vitamin B12 has also been investigated for its effects on various sleep disorders. Despite the findings of earlier researchers who found vitamin B12 useful at regulating sleep-wake rhythm disorders (Kiuchi et al., 1997; Yamadera et al., 1996), Okawa et al. found no such association in a study conducted in 1997 (Okawa et al., 1997).

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References

1.      Dietary Supplement Fact Sheet: Vitamin B12.  Office of Dietary Supplements; National Institutes of Health.Reviewed June 24, 2011; Accessed April 23, 2012.

2.      What is Pernicious Anemia?  National Heart Lung and Blood Institute. April 1, 2011; Accessed April 23, 2012.

3.      Clarke R. B-vitamins and prevention of dementia. Proc Nutr Soc. 2008;67:75-81.

4.      Institute of Medicine (IOM). Food and Nutrition Board. Dietary Reference Intakes: Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Washington, DC: National Academy Press, 1998.

5.      Johnson MA. If high folic acid aggravates vitamin B12 deficiency what should be done about it? Nutr Rev. 2007;65:451-458.

6.      Abeles AM, Pillinger MH, Solitar BM, Abeles M. Narrative review: the pathophysiology of fibromyalgia. Ann Intern Med. 2007;146:726–734.

7.      Russell IJ, Vaeroy H, Javors M, Nyberg F. Cerebrospinal fluid biogenic amine metabolites in fibromyalgia/fibrositis syndrome and rheumatoid arthritis. Arthritis Rheum. 1992:35:550–556.

8.      Legangneux E, Mora JJ, Spreux-Varoquaux O, Thorin I, Herrou M, Alvado G et al. Cerebrospinal fluid biogenic amine metabolites, plasma-rich platelet serotonin and [3H]imipramine reuptake in the primary fibromyalgia syndrome. Rheumatology (Oxford). 2001;40:290–296.

9.      Ortancil O, Sanli A, Eryuksel R, Basaran A, Ankarali H. Association between serum ferritin level and fibromyalgia syndrome. Eur J Clin Nutr. 2010;64(3):308-312.

10.  Ellis FR, Nasser S. A pilot study of vitamin B12 in the treatment of tiredness. Br J Nutr. 1973;30:277-283.

11.  Gaby AR. Intravenous nutrient therapy: the “Myers’ Cocktail.” Altern Med Rev. 2002;7(5):389-403.

12.  Sachdev PS, Parslow RA, Lux O, Salonikas C, Wen W, Naidoo D, Christensen H, Jorm AF. Relationship of homocysteine, folic acid, and vitamin B12 with depression in a middle-aged-community sample. Pyschol Med. 2005;35(4):529-538.

13.  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):301-307.

14.  Coppen A, Bolander-Gouaille C. Treatment of depression: time to consider folic acid and vitamin B12. J Psychopharmacol. 2005;19(1):59-65.

15.  Tiemeier H, Van Tuijl HR, Hofman A, Meijer J, Kiliaan AJ, Breteler MM. Vitamin B12, folate, and homocysteine in depression: the Rotterdam Study. Am J Psychiatry. 2002;159(12):2099-2101.

16.  Ford A, Flicker L, Thomas J, Norman P, Jamrozik K, Almeida OP. Vitamins B12, B6, and folic acid for onset of depressive symptoms in older men: results from a 2-year placebo-controlled randomized trial. J Clin Psychiatry. 2008;69: 1203-1209.

17.  Bottiglieri T, Laundy M, Crellin R, Toone BK, Carney MW, Reynolds EH. Homocysteine, folate, methylation, and monoamine metabolism in depression. J Neurol Neurosurg Psychiatry. 2000; 69:228-232.

18.  Tangney CC, Aggarawal NT, Li H, Wilson RS, Decarli C, Evans DA, Morris MC. Vitamin B12, cognition, and brain MRI measures: a cross-sectional examination. Neurology. 2011;77(13):1276-1282.

19.  McCracken C. Challenges of long-term nutrition intervention studies on cognition: discordance between observational and intervention studies of vitamin B12 and cognition. Nutr Rev. 2010;68(Suppl 1):S11-S15.

20.  Moretti R, Torre P, Antonello RM, Cattaruzza T, Cazzato G, Bava A. Vitamin B12 and folate depletion in cognition: a review. Neurol India. 2004;52(3):310-318.

21.  Malouf R, Areosa Sastre A. Vitamin B12 for cognition. Cochrane Database Syst Rev. 2003;(3):CD004326.

22.  Okawa M, Takahashi K, Egashira K, Furuta H, Higashitani Y, Higuchi T, Ichikawa H, Ichimaru Y, Inoue Y, Ishizuka Y, Ito N, Kamei K, Kaneko M, Kim Y, Kohsaka M, Komori T, Kotorii T, Matsumoto M, Mishima K, Mizuki Y, Morimoto K, Nagayama H, Ohta T, Okamoto N, Takahashi S, et al. Vitamin B12 treatment for delayed sleep phase syndrome: a multi-center double-blind study. Psychiatry Clin Neurosci. 1997;51(5):275-279.

23.  Kiuchi T, Sei H, Seno H, Sano A, Morita Y. Effect of vitamin B12 on the sleep-wake rhythm following an 8-hour advance of the light-dark cycle in the rat. Physiol Behav. 1997;61(4):551-554.

24.  Yamadera H, Takahashi K, Okawa M. A multicenter study of sleep-wake rhythm disorders: therapeutic effects of vitamin B12, bright light therapy, chronotherapy, and hypnotics. Psychiatry Clin Neurosci. 1996;50(4):203-209.

 

 

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