Carnitine and Fibromyalgia
Carnitine is a compound naturally produced in the liver and kidneys as certain proteins are metabolized. It is essential for energy production and works to transport fat to cells, where it is then burned for energy. In addition, carnitine helps cells excrete the toxic byproducts of metabolism, thereby maintaining cell health and longevity. It can be found in almost every cell of the human body, however it is most concentrated in the bones and heart muscle.
The body naturally produces two forms of carnitine: L-carnitine and D-carnitine, however only the L-carnitine form can be used by the body. Supplemental carnitine is available in three forms: L-carnitine, acetyl-L-carnitine, and L-propionyl carnitine. Of these, only the L-carnitine and acetyl-L-carnitine versions are available in the United States. In the body, both L-carnitine and acetyl-L-carnitine work in the same manner to transport fat to cells; however, acetyl-L-carnitine is absorbed quicker and more efficiently in the intestines than its L-carnitine counterpart.
For most people, the body is able to produce enough carnitine to meet daily needs, therefore most healthy children and adults do not need to consume extra carnitine from food or dietary supplements. As such, there is no Recommended Dietary Allowance (RDA) established for carnitine. Some individuals, however, may not be able to produce enough on their own. This includes people with certain genetic problems or medical conditions. In these instances, deficiency may result. Carnitine deficiency can occur in two ways. Primary carnitine deficiency occurs as a result of a genetic disorder that normally appears by the age of five and is characterized by heart muscle disease, skeletal muscle weakness, and low blood sugar. Secondary carnitine deficiency can result from conditions such as chronic kidney failure or occur under specific circumstances that reduce the body’s ability to absorb or increase its excretion of carnitine. For example, treatment with certain types of antibiotics can cause this to happen.
Both L-carnitine and acetyl-L-carnitine supplements can adversely interact with several anticoagulant (blood-thinning) drugs, including acenocoumarol (Sintrom) and warfarin (Coumadin) (Martinez et al., 1003; Bachmann & Hoffmann, 2004). Acetyl-l-carnitine supplementation can have the most serious interactions, in particular with acenocoumarol, and therefore these two should not be taken in combination. L-carnitine supplements may also decrease the effectiveness of certain thyroid hormone medications (Benvenga et al., 2001; Benvenga et al. 2004). In addition, concurrent use of a D-carnitine supplement may result in symptoms of L-carnitine deficiency, therefore individuals should avoid taking both supplements at the same time (Tosko et al. 1995; Wu et al., 1999).
Oral and intravenous use of L-carnitine has been associated with a number of side effects, including nausea, vomiting, abdominal cramping, heartburn, stomach upset, and seizures (Carnitor package insert). The urine, breath, and sweat of those who consume both L-carnitine and acetyl-l-carnitine supplements may take on a fishy odor (Evans & Fornasini, 2003). When consumed orally, acetyl-L-carnitine is usually well-tolerated with few side effects (Hudson & Tabet, 2003), although nausea, vomiting, stomach upset, and restlessness may occur in some individuals (Evans & Fornasini, 2003).
Supplemental L-carnitine and acetyl-L-carnitine have been widely studied across a number of conditions and for a variety of therapeutic uses. L-carnitine has been demonstrated to be possibly effective at improving symptoms associated with a variety of cardiac conditions, including chronic stable angina (stress- or activity-related chest pain), congestive heart failure, and myocarditis (inflammation of the heart muscle) (Ramos et al., 1992; Ramos et al., 1984; Cacciatore et al., 1991; Sherchi et al., 1985; Rizos 2000; Ghidini et al., 1988).
Fatigue is a hallmark symptom of fibromyalgia, however few studies have investigated the use of L-carnitine supplementation to reduce fatigue in fibromyalgia patients. A number of studies have, however, investigated the relationship between carnitine supplementation and relief of fatigue among individuals with age-related fatigue, celiac disease, and multiple sclerosis. Although insufficient evidence is currently available to conclusively determine the overall effectiveness of L-carnitine supplementation for fatigue related to these conditions, encouraging findings have been reported. Among elderly patients, preliminary research suggests that L-carnitine supplementation over a 30 day period improves both physical and mental fatigue, and improves overall body composition (Pistone et al., 2003; Malaguarnera et al., 2007). Some research studies have found low levels of L-carnitine in individuals with Celiac disease. Preliminary clinical research studies have also reported improvements in measures of fatigue with daily consumption of L-carnitine supplements over a six month period; however, no significant improvements were observed with regard to depression or quality of life (Ciacci et al., 2007). Similar findings have also been observed for multiple sclerosis patients with low blood levels of L-carnitine (Lebrun et al., 2006).
Cognitive impairment, or “fibro fog” is another extremely common symptom associated with fibromyalgia. Although no research exists related to the role of carnitine deficiency in the development of cognitive impairment in fibromyalgia (or supplementation as a means by which to improve symptoms), acetyl-L-carnitine has been widely investigated as a means of improving cognitive impairment in a variety of other populations, as well as in Alzheimer’s disease patients. For example, research has demonstrated that oral acetyl-L-carnitine supplementation improves some measures of cognitive function and memory capacity in older individuals with age-related cognitive decline (Cicomptta et al, 1988; Salvioli & Neri, 1994; Passeri et al., 1990). Furthermore, acetyl-l-carnitine may be useful to help slow the rate of disease progression, improve memory and cognitive functioning, and behavioral performance in certain subsets of Alzheimer’s patients (Thal et al., 1996; Sano et al., 1992; Spagnoli et al., 1991; Brooks et al., 1998; Pettegrew et al., 1995; Rai et al., 1990). In addition to age- and Alzheimer’s- associated cognitive impairment, acetyl-l-carnitine has also shown promise as a treatment for cognitive deficits in alcoholics (Tempesta et al., 1990).
Finally, several groups of researchers have examined the role acetyl-l-carnitine plays in reducing the symptoms associated with diabetic neuropathy (nerve damage resulting from high blood sugar levels) in certain groups of diabetic patients. Studies have shown that individuals with both type-1 and type-2 (adult-onset) diabetes experience improvements in neuropathy symptoms following sustained consumption of acetyl-L-carnitine over a year. Findings suggest that acetyl-l-carnitine increases the number of nerve fibers, helps damaged nerve fiber clusters to regenerate (re-grow), and improves sensations. In addition, individuals who had neuropathic pain also experienced decreases in their neuropathy-related pain within six months of starting treatment with acetyl-L-carnitine.
Carnitine and Fibromyalgia Research
Although none of the research described above relates specifically to fibromyalgia patients, it does address a number of symptoms and comorbidities that are quite common in fibromyalgia, including fatigue, Celiac disease, cognitive impairment, and neuropathic pain, and therefore may suggest potential new avenues for fibromyalgia research. For example, while diabetic neuropathy is, by definition, not related to fibromyalgia (although some fibromyalgia patients may have diabetes and thus also have associated neuropathy), the research that has emerged regarding the role acetyl-L-carnitine plays in the health and functioning of nerve fibers may eventually prove useful in understanding the central nervous system’s role in the development of fibromyalgia. Additionally, the promising observations seen with the use of acetyl-l-carnitine to improve age- and Alzheimer’s-related cognitive decline may be of similar benefit to future research efforts related to fibromyalgia-associated cognitive impairment.
Very few research studies have directly examined the association (if any) between fibromyalgia and carnitine from either a preventative or treatment perspective. A 2007 article published by Rossini et al. conducted a randomized placebo-controlled trial to evaluate the effectiveness of acetyl-L-carnitine in patients with fibromyalgia. They enrolled 152 patients with fibromyalgia (all of whom were diagnosed using the American College of Rheumatology criteria for fibromyalgia). Study subjects were randomly assigned to receive either two oral capsules per day of 500mg acetyl-L-carnitine, a placebo, or an intramuscular injection of 500mg acetyl-L-carnitine or placebo for a period of two weeks. For the following eight weeks, subjects consumed three capsules per day of either 500 mg acetyl-L-carnitine or a placebo. The study evaluated the impact on the number of each subject’s positive tender points, pain threshold, self-perceived stiffness, fatigue, tiredness upon awakening, employment status, depression, musculoskeletal pain, and depression.
During the first six weeks of the study, the number of positive tender points and overall pain threshold declined at similar rates, and significantly, in both groups. At the 10th week of treatment, these variable remained steady in the placebo group but those receiving acetyl-L-carnitine supplements continued to see significant improvements. In addition, the acetyl-L-carnitine group also showed greater improvements in depression and musculoskeletal pain. In their discussion, the authors note the need for future research to investigate the role of acetyl-L-carnitine in pain control for fibromyalgia patients (Rossini et al., 2007).