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Treatments for CMT

 Vitamin C - Ascorbic acid is an organic acid with antioxidant properties. The L-enantiomer of ascorbic acid is also known as vitamin C. The name "ascorbic" comes from its property of preventing and curing scurvy. Ascorbate acts as an antioxidant by being itself available for energeticaly favourable oxidation. Studies reveal that vitamin C aids in proper myelin formation in peripheral nerves (5). A German study in 2006 showed that ascorbic acid reduced demyelination and premature death in a mouse model of CMT1A(6). An ongoing in  Italy is studying the effect of 1500mg of vitamin C/day in CMT patients (7).

4.      Padma - There is increasing evidence of an autoimmune component in CMT. There appears to be increased activation of cytotoxic lymphocytes as well as evidence for increased pro-inflammatory metabolites of arachidonic acid (8,9,10). A 2005 German study revealed macrophages (white blood cells who's role is to phagocytize (engulf and then digest) cellular debris and pathogens either as stationary or mobile cells, and to stimulate lymphocytes and other immune cells to respond to the pathogen) attacking myelin in a mouse model on CMT (11). This evidence suggest the use of an herbal compound such as Padma to quiet the immune activity in CMT. 

      A number of countries, including Switzerland, Poland, Austria, Israel  and the United 

States have studied Padma 28, an herbal mixture of 25 herbal constituents combined in a specific order with strict weight ratios. It is has been used for centuries in Tibetan medicine. Its efficacy in various disorders is related to modulation of immunological function. Several studies, including an Israeli study in 1995, suggest an anti-inflammatory 

effect. Padma inhibits lysozyme (a substance that breaks down tissue) release from stimulated human neutrophils and reduces nitric oxide production in macrophages. Nitric oxide is a small and pervasive molecule in the body that can be involved in inflammatory processes. Two of the constituents of Padma 28, costus root (the dried root of Saussurea chebula) and myrobalani fructus (the dried fruit of Terminalia chebula), by themselves inhibited nitric oxide production. A 1999 study in the US showed that Padma 28 had

                         a dose-dependent effect against EAE in mice. The authors suggest that the protective effect could best be explained by a broad protective mechanism of action referred to as nonspecific resistance (NSR) to diverse biological and psychological stressors. The class of herbs or substances exhibiting these properties is called adaptogens or bioprotectants. A Polish study in 1982 showed improved suppressor cell function in T lymphocytes exposed to Padma 28.Suppressor cells are a subset of lymphocytes involved in inhibiting inflammatory reactions. The study revealed improved differentiation and maturation of the suppressor cell subset of T lymphocytes.

                         Padma is safe and its properties suggest a beneficial effect in CMT. Dose is 2-3 tablets twice/day.

 

5.  Essential fatty acids – the activation of arachidonic acid and the omega 6 metabolites of arachidonic acid suggest a benefit of supplementation with the anti-inflammatory omega three fatty acids.  The most important omega three fatty acids, EPA and DHA, reduce a number of proinflammatory substances in the body including prostaglandin E2, and substances secreted by white blood cells including leukotriene B4 and other proinflammatory cytokines. In addition, EPA and DHA are precursors to the anti-inflammatory prostaglandin 3 series. DHA may be the most critical essential fatty acid for nerve cell membranes, including myelin, the coating around nerves. A 1986 study supplementing CMT patients with essential fatty acids and vitamin E revealed neurologic improvement which continued for a year after the placebo period ended (12). The author recommends that CMT patients supplement with heavy metal free fish oil. Dose is approximately 500mg EPA plus DHA twice/day.

 

6.  Phosphatidylserine – A phospholipid that is an essential component in nerve cell membranes and myelin. It is a basic structural component and is also involved in signal transduction. DHA, discussed above is important as a metabolic precursor of phosphatidyl serine. There are a number of studies showing benefit of phosphatidylserine in cognition. Although there are no clinical studies in CMT, its importance in myelin and in information signaling suggests a potential benefit in CMT.

 

7.  Vitamin E - Natural vitamin E is a fat soluble vitamin that exists in eight different forms or isomers, four tocopherols and four tocotrienols. It is an important anti-oxidant in the lipid or fat soluble compartments of the body. This includes the nervous system, a highly fatty tissue. Immune cells, such as the macrophages, decompose their targets with a highly pro-oxidant discharge of free radicals. As noted above, the immune system plays a role in myelin destruction in CMT. Vitamin E would provide a natural form of protection for myelin against free radical injury. An appropriate dosage is 400 IU/day.

 

8. Alpha lipoic acid - Alpha-lipoic acid is a very important antioxidant. It is both water and fat-soluble, enters the nervous system easily, reduces vitamins C and E from their oxidized state (making them reusable), and increases intracellular levels of glutathione, a critical intracellular antioxidant. Given the potential value of vitamin C and E in CMT, the addition of alpha lipoic acid is important in keeping C and E in their reduced or anti-oxidant form. Dosage for alpha-lipoic acid is 300mg/day of a sustained release formulation.

 

9.  Vitamin B12 - The name vitamin B12 is used in two different ways. In a broad sense it refers to a group of cobalt-containing compounds known as cobalamins - cyanocobalamin (an artifact formed as a result of the use of cyanide in the purification procedures), hydroxocobalamin and the two coenzyme forms of B12, methylcobalamin (MeB12) and 5-deoxyadenosylcobalamin (adenosylcobalamin - AdoB12). It is know that B12 deficiency causes demyelination. The exact mechanism of B12’s role in preserving myelin is not known. Due to its complete safety, and its role in the protection of myelin, B12 supplementation is recommended in CMT. Suggested dosage is 1 mg/day.

 

10.   Although there are no studies confirming the efficacy of different herbs in CMT,  their traditional usage suggest a potential tole in CMT. The following five herbs are presented here for their potential value in CMT

 

Ginkgo - Ginkgo biloba, also called maidenhair tree, is thought to predate the ice age, the sole remaining species of the entire ginkophyte botanical division flourishing 250 million years ago. The kernel has been used for several thousand years in Chinese medicine, while the leaf is a very recent addition to herbal medicine. Constituents include diterpenoid lactones-gingolide A,B,C; sesquiterpene - bilobalide, flavone glycosides - kaempferol, quercetin, isochamnetin; and tannins. There are more than 300 studies on ginkgo, including 40 clinical trials. Ginkgo has multiple pharmacologic effects including enhancing microcirculation, increasing blood fluidity, increasing tissue oxygen utilization, stabilizing blood-brain barrier and reducing cerebral edema, reducing platelet aggregation, antioxidant effect, and increasing dopaminergic, cholinergic and serotoninergic function. Experiments also show improved motor nerve regeneration.

             St. John’s Wort - Hypericum perforatum is a perennial plant with bright yellow flowers. Hypericum, or “over an apparition”, makes reference to the historical use in exorcising ghosts, while perforatum refers to the tiny translucencies in the leaves that can be seen when holding the leaf to the sun. It’s use dates back over the centuries to ancient Greece, with topical use for wounds and burns, and oral use for kidney and lung ailments as well as depression. The plant contains a red pigment, hypericin, along with essential oils, phenolic carboxylic acids, carotenoids, alkanes, phytosterols, phloroglucin derivatives, medium-chain fatty acids, flavonoids, xanthones and pseudohypericin. It has antimicrobial effects against multiple viruses including herpes simplex type 1 and 2, influenza type A and B, CMV, E-B virus, hepatitus B and retroviruses as well gram positive and negative bacteria. Originally conjectured to have clinical MAO inhibitory activity, the actual antidepressant mechanism is unknown. Its anti-depressant effect is well established. It is anti-inflammatory, and considered a vulnerary, or wound healer for the nervous system.

Ashwaghanda – an adaptogen in Ayur Vedic medicine that promotes sleep, adaptation to stress, is anti-inflammatory and rejuvenating. It increased strength in a clinical trial in children. It is considered a nervine in Ayur Vedic medicine.

 Bacopa – the foremost nerve tonic in Ayur Vedic medicine. Reported to improve memory, learning and concentratrion. It improved motor efficiency in rat studies.

Wild Oats – considered a nutritive herb for the nervous system.