One hundred and two patients with fibromyalgia were randomly assigned to receive,
in double-blind fashion, acetyl L-carnitine (ALC) or placebo for ten weeks.
During the first two weeks, patients received daily 1,000 mg orally and 500
mg intramuscularly. During the next eight weeks, the patients received 1,500
mg per day orally. After ten weeks, the improvements in depression, musculoskeletal
pain, number of tender points, and total symptom score were significantly
greater in the ALC group than in the placebo group. No significant difference
was seen between groups after six weeks. ALC was well-tolerated.
Comment: These findings suggest that ALC
is an effective treatment for fibromyalgia, although treatment has to be
continued for a substantial period of time before
improvement is seen. It is probably not necessary to begin treatment with intramuscular
injections, as was done in the present study, since orally administered ALC
has demonstrated a wide range of beneficial effects, including improvement
in memory, fatigue, and Peyronie's disease. While the mechanism of action
of ALC is not clear, it appears to function as a neurotransmitter. In addition,
the carnitine component of ALC may enhance energy metabolism by promoting the
uptake of fatty acids into mitochondria. ALC is generally well-tolerated, although
it was reported in one study to cause nausea and vomiting in more than one-quarter
of patients with Alzheimer's disease.
et al. Double-blind, multicenter trial comparing acetyl l-carnitine
with placebo in the treatment of fibromyalgia patients.
Clin Exp Rheumatol. 2007;25:182-188.
Intravenous vitamins and minerals for fibromyalgia
Seven patients with treatment-resistant fibromyalgia, with disease duration
of at least eight years, received an intravenous infusion of nutrients once
a week for eight weeks. Each infusion contained 400 mg of magnesium chloride
hexahydrate, 40 mg of calcium gluconate, 3,000 mg of vitamin C, 1,000 mcg
of hydroxocobalamin, 100 mg of pyridoxine hydrochloride, 250 mg of dexpanthenol,
2 mg of riboflavin, 100 mg of thiamine, and 100 mg of niacinamide. The nutrients
were administered in 100 ml of normal saline over a period of 20-30 minutes.
All patients reported an improvement in pain and fatigue by the second treatment.
At the end of the treatment period, there was a 60% reduction in the mean
pain severity (p = 0.005) and an 80% decrease in the mean level of fatigue
(p = 0.005). No patient reported complete or lasting resolution of pain or
fatigue. No side effects were reported.
Comment: In my experience with approximately
30 fibromyalgia patients given a treatment similar to the one described above,
some (perhaps 25%) became pain-free
(Gaby AR. Altern Med Rev. 2002;7:389-403.). Most of my patients received more
magnesium chloride hexahydrate (800 mg vs. 400 mg) and calcium gluconate (200
mg [2 ml of a 10% solution] vs. 40 mg) in their infusion than did those in
the present study. In addition, the usual infusion rate for my patients was
five to 15 minutes, depending on their tolerance. In contrast, the patients
in the present study received the infusion over 20-30 minutes. While there
are risks associated with too-rapid infusion of magnesium and other nutrients,
the higher peak serum nutrient concentrations that occur with more rapid administration
may result in enhanced cellular nutrient uptake and a greater therapeutic effect
in some cases.
Massey PB. Reduction of fibromyalgia symptoms
through intravenous nutrient therapy: results of a pilot clinical
trial. Altern Ther
Health Med. 2007;13(3):32-34.
D-ribose for fibromyalgia/chronic fatigue syndrome
Forty-one patients (mean age, 48 years) with fibromyalgia and/or chronic fatigue
syndrome received, in open-label fashion, D-ribose at a dose of 5 g, three
times per day, for a total of 280 g. Significant improvements were seen in
all five visual analog scale categories assessed: energy, sleep, mental clarity,
pain intensity, and well-being. The absolute improvement on a 1 to 10 scale
for the different parameters assessed ranged from 0.7 to 1.7. Side effects
included anxiety (n = 1), lightheadedness (n = 1), and increased appetite
(n = 1).
Comment: Fibromyalgia and chronic fatigue syndrome are associated with impaired
cellular energy metabolism. D-ribose has been shown to increase energy production
in the heart and skeletal muscle by providing a substrate for the synthesis
of adenine nucleotide, which is, in some circumstances, a rate-limiting factor
for the production of ATP. While the results achieved with ribose supplementation
were modest, this compound might be useful when used as a component of a comprehensive
Teitelbaum JE, et al. The use of D-ribose in
chronic fatigue syndrome and fibromyalgia: a pilot study. J
Altern Complement Med. 2006;12:857-862.
Folinic acid for chronic fatigue syndrome and fibromyalgia
Forty-two patients (aged 19-64 years) with chronic fatigue syndrome, with or
without fibromyalgia, received 25 mg of folinic acid three to four times
per day for one to two months. Thirty-four patients (81%) reported a significant
increase in energy level and a reduction in pain within two months. No adverse
effects were reported. Responses were seen both in patients with primary
fibromyalgia and fatigue and in those whose condition was associated with
other diseases such as rheumatoid arthritis, systemic lupus erythematosus,
inflammatory bowel disease, or multiple sclerosis.
Comment: Folinic acid (5-formyl tetrahydrofolate) is an activated form of folic
acid. In certain circumstances, when the conversion of folic acid to its active
forms is blocked, folinic acid is an effective treatment even though folic
acid is not. In addition, some people have a defect in the transport of folic
acid across the blood-brain barrier into the brain, because they make antibodies
that block the folate receptors in the choroid plexus. In those people, treatment
with folinic acid corrects cerebral folate deficiency by bypassing the folic
acid transport mechanism. There is no clear evidence that people with fibromyalgia
or chronic fatigue syndrome have a defect in folic acid absorption, transport,
or utilization. However, considering the apparent effectiveness of folinic
acid in the treatment of these conditions, such a possibility should be investigated.
Controlled trials are needed to confirm the efficacy of folinic acid.
Lundell K, et al. Clinical activity of folinic
acid in patients with chronic fatigue syndrome. Arzneimittelforschung.
Preventing complex regional pain syndrome with
Four hundred and sixteen patients with 427 wrist fractures were randomly assigned
to receive, in double-blind fashion, placebo or vitamin C (200, 500, or 1,500
mg/day) for 50 days. The incidence of complex regional pain syndrome was 76%
lower in the vitamin C group than in the placebo group (2.4% vs. 10.1%; p =
0.002). All of the affected patients were elderly women. The incidence was
4.2% in the 200-mg vitamin C group, 1.8% in the 500-mg group, and 1.7% in the
1500-mg group. Thus, vitamin C in doses of at least 500 mg/day decreased the
incidence of complex regional pain syndrome by 82%.
Comment: Complex regional pain syndrome (previously called reflex sympathetic
dystrophy) is characterized by chronic burning pain, often accompanied by trophic
skin changes. It results from injury to a peripheral nerve. The condition is
difficult to treat and results in significant morbidity and lost time from
work. Previous studies have shown that supplementation with vitamin C reduces
microvascular leakage of fluid and proteins following skin burns. Circumstantial
evidence suggests that microvascular abnormalities may also be involved in
the pathogenesis of complex regional pain syndrome. The results of the present
study confirm a previous report that vitamin C supplementation following trauma
can prevent complex regional pain syndrome. The authors of this study recommend
a dose of 500 mg/day for 50 days, although their data suggest that a higher
dose might be slightly more effective. Flavonoids also improve capillary integrity,
so supplementation with flavonoids might enhance the preventive effect of vitamin
Zollinger PE, et al. Can vitamin C prevent complex
regional pain syndrome in patients with wrist fractures? A randomized,
study. J Bone Joint Surg Am. 2007;89:1424-1431.
Thyroiditis as a cause of chronic fatigue
Two hundred and nineteen patients with a history of chronic fatigue for more
than one year underwent fine-needle aspiration of the thyroid gland. Forty
percent of the patients had definite histological evidence of chronic lymphocytic
(autoimmune) thyroiditis. In the patients with autoimmune thyroiditis, Thyroid
Stimulating Hormone (TSH) levels were widely scattered, with a median value
of 3.8 mU/L (range, < 0.9 to > 15 mU/L). Administration of levothyroxine
to the patients with autoimmune thyroiditis resulted in clinical improvement,
irrespective of the initial TSH level. Of note, only about half of the patients
with histologic evidence of autoimmune thyroiditis had elevated serum levels
of thyroid autoantibodies (peroxidase or thyroglobulin).
Comment: These findings indicate that chronic autoimmune thyroiditis is common
among people with chronic fatigue; that patients with autoimmune thyroiditis
improve after treatment with levothyroxine, even if their laboratory tests
for thyroid function are normal; and that measuring thyroid autoantibodies
in the blood will fail to detect thyroiditis in half of these individuals.
I have found that clinical evaluation can identify, with a reasonable degree
of reliability, those patients with normal thyroid function tests who are likely
to show a positive response to thyroid hormone. A careful medical history and
physical exam may obviate the need for an invasive thyroid biopsy in many patients
in whom hypothyroidism is suspected. (For additional information, see Gaby
AR. "Sub-laboratory" hypothyroidism and the empirical use of Armour
thyroid. Altern Med Rev. 2004;9:157-179.).
Wikland B, et al. Fine-needle aspiration cytology
of the thyroid in chronic fatigue. Lancet. 2001;357:956-957.
Wikland B, et al. Subchemical hypothyroidism. Lancet. 2003;361:1305.
Allergy to folic acid
In a case report, a woman had three episodes of allergic reactions, including
anaphylaxis, after ingesting synthetic folic acid. Intradermal testing with
folic acid was positive. A graded, blinded challenge with a folic acid solution
led to widespread urticaria at a dose of 160 mcg. The patient appeared to
tolerate dietary folates (pteroylpolyglutamates).
Comment: Although allergy to synthetic folic acid is rare, it is likely to
become a more common clinical entity now that grains are being fortified with
this vitamin. Folic acid allergy should be considered in the differential diagnosis
of idiopathic anaphylaxis and in patients with suspected grain allergy.
Smith J, et al. Recurrent anaphylaxis to synthetic
folic acid. Lancet. 2007;370:652.
Can vitamin D help you live longer?
The risk of dying from any cause was examined in a pooled analysis of 18 randomized
trials (including a total of 57,311 participants) of vitamin D2 or vitamin
D3 supplementation. In most of the trials, the primary outcome measure was
related to the prevention or treatment of osteoporosis or the prevention
of falls. The mean vitamin D dose in the trials was 528 IU/day. During a
mean follow-up period of 5.7 years, 4,777 deaths occurred. The pooled relative
risk for mortality from any cause was 0.93 (95% CI, 0.87-0.99). The relative
risk was not influenced by the inclusion of calcium supplements in the trial.
Comment: The results of this study indicate that supplementation with relatively
modest doses of vitamin D can decrease the risk of death from any cause by
seven percent. Some of this reduction in mortality may be due to prevention
of hip fractures, which are associated with a relatively high five-year mortality
rate. There is evidence that vitamin D may also reduce the incidence of certain
types of cancer. In addition, vitamin D supplementation appears to improve
glucose metabolism in people with diabetes and might therefore reduce the risk
of fatal diabetic complications such as renal failure and heart disease. In
addition to keeping you alive, extra vitamin D may help you maintain a sunny
disposition ("Sunshine on my shoulder makes me happy").
Autier P, Gandini S. Vitamin D supplementation
and total mortality: a meta-analysis of randomized controlled trials.
Arch Intern Med.
by Alan R. Gaby, MD