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Can Alpha-Lipoic Acid Improve Multiple Sclerosis?
Introduction
Multiple sclerosis is a syndrome of progressive nerve disturbances that
usually occurs early in adult life. It is caused by gradual loss of the
myelin sheath that surrounds the nerve cell. This process is called demyelination.
One of the key functions of this myelin sheath is to facilitate the transmission
of the nerve impulse. Without the myelin sheath, nerve function is lost.
Symptoms correspond to the nerves that have lost their myelin sheath.
Sudden transient motor and sensory disturbances, including blurred vision,
dizziness, muscle weakness, and tingling sensations. The diagnosis is
confirmed by the detection of evidence of demyelination on magnetic resonance
imaging (MRI).
MS is an autoimmune disease – a disease where the immune system
attacks body tissues as foreign proteins. Damage to nerve cells as a result
of free radicals is thought to be a major trigger for the autoimmune process.
Free radicals are highly reactive molecules that can bind to cellular
compounds and destroy them. In MS, free radical damage exposes cellular
components that are normally hid to the immune systems thereby initiating
the formation of antibodies to these components. Free radicals have also
been implicated in the activation of matrix metalloproteinase (MMP), which
is an important mediator of white blood cell transport into the central
nervous system (CNS), i.e., the brain and spinal cord. In order for MS
to progress, white blood cells must enter the CNS.
Alpha-lipoic acid
Alpha-lipoic acid (alpha-LA) is a vitamin-like substance that is often
described as “nature’s perfect antioxidant.”1 It is
given this title because it is a very small molecule that is efficiently
absorbed and easily crosses cell membranes including the blood brain barrier.
Unlike vitamin E which is primarily fat soluble and vitamin C which is
water soluble, alpha-LA can quench either water or fat soluble free radicals
both inside the cell and outside in the intracellular spaces. Furthermore,
alpha-LA extends the biochemical life of vitamin C and E as well as other
antioxidants.
The primary clinical use of alpha-lipoic acid has been for the treatment
of diabetic neuropathy. In fact, it has been successfully used in Germany
for over thirty years as an approved drug for this condition. The beneficial
effects of alpha-LA in diabetic neuropathy have been confirmed in numerous
double-blind studies at a dosage of 300 to 600 mg daily.
Alpha-lipoic acid in MS
Alpha-lipoic acid (ALA) has shown the ability to suppress and treat
the animal model of MS, experimental autoimmune encephalomyelitis(EAE).
These animal studies have led to further investigations. In the initial
phase of lesion formation in EAE as well as MS, reactive oxygen species
of free radicals cause damage to the blood brain barrier (BBB). Normally,
this protective barrier prevents the passage of large molecules as well
as white blood cells into the CNS. Once the BBB is damages it leads to
the migration of T lymphocytes and other white blood cells into the CNS.
Alpha-LA has been shown to produce a dose-dependent ability to prevent
the development of clinical signs in EAE in rats through its ability to
decrease in white blood cell infiltration into the CNS. A dose-dependent
ability means that alpha-LA effect increases as dosage increases. In addition,
using live cell imaging techniques, researchers also visualized and quantitatively
assessed that alpha-LA also exerts a direct ability to stabilize the BBB.
In addition, alpha-LA has also shown the ability to inhibit the formation
of a variety of compounds associated with promoting inflammation within
the CNS and their inhibition provides another mechanism to explain the
observed effects of alpha-LA in EAE.2-4
Clinical Research Supports use of alpha-LA
in MS
A study was recently conducted that sought to determine the effects of
ALA in patients with MS.5 Thirty-seven MS subjects were randomly assigned
to one of four groups: placebo, alpha-LA 600 mg twice a day, alpha-LA
1200 mg once a day and alpha-LA 1200 mg twice a day. Subjects took the
capsules for only 14 days. The pharmacokinetic data indicated that subjects
taking 1200 mg alpha-LA had substantially higher peak serum alpha-LA levels
than those taking 600 mg and that peak levels varied considerably among
subjects. In other words, some people may require more alpha-LA than others
to see clinical benefit. The higher the level of alpha-LA, the greater
the reduction in matrix metalloproteinase 9 levels (MMP-9). This compound,
MMP-9, is associated with disease activity in MS. Therefore, the higher
dosage of alpha-LA, the greater the clinical benefit. There was also a
significant dose response relationship between alpha- LA and the adhesion
molecule that helps transports white blood cells into the CNS. The researchers
concluded that alpha-LA is well tolerated and appears to be a useful adjunct
in the treatment of MS.
Final Comments
MS is definitely a “multi-factorial” disease meaning that
in order to effectively halt its progression many different factors must
be addressed (for more information see http://www.doctormurray.com/conditions/Multiple_Scelerosis.asp
). These recent studies with alpha-LA indicate that it certainly is
an important therapeutic tool. In MS, the effective dosage appears to
be in the range of 1,200 mg daily.
Key references:
- Moini H, Packer L, Saris NE. Antioxidant and prooxidant activities
of alpha-lipoic acid and dihydrolipoic acid. Toxicol Appl Pharmacol
2002;182:84-90.
- Marracci GH, Jones RE, McKeon GP, Bourdette DN. Alpha lipoic acid
inhibits T cell migration into the spinal cord and suppresses and treats
experimental autoimmune encephalomyelitis. J Neuroimmunol 2002;131:104-114
- Schreibelt G, Musters RJ, Reijerkerk A, et al. Lipoic Acid affects
cellular migration into the central nervous system and stabilizes blood-brain
barrier integrity. J Immunol. 2006;177(4):2630-7.
- Chaudhary P, Marracci GH, Bourdette DN. Lipoic acid inhibits expression
of ICAM-1 and VCAM-1 by CNS endothelial cells and T cell migration into
the spinal cord in experimental autoimmune encephalomyelitis. J Neuroimmunol.
2006;175(1-2):87-96.
- Yadav V, Marracci G, Lovera J, et al. Lipoic acid in multiple sclerosis:
a pilot study. Mult Scler. 2005;11(2):159-65.
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