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Can Alpha-Lipoic Acid Improve Multiple Sclerosis?
By Michael T. Murray N.D.
October 18, 2006
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-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.
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.
- 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