Annemarie, you do know that with your avonex induced liver problems you are going to find it very difficult to find a doctor of any persuasion to treat you. You will certainly need someone locally who can keep a check on you. To give you a head start, make sure that the first supplements you make sure of taking are N-acetyl cysteine and Acetyl L-carnitine. I have cut and pasted the details from David's relevant page below. You can obtain both in high quality, high dosage but reasonably priced amounts from here: http://www.iherb.com/index.html
I cannot stress this need enough. However, with these and the LDN you might well be amazed at how well you do. Keep in touch.
N-acetyl cysteine ~ Selenium
Reduced glutathione (GSH) neutralizes peroxides in the presence of a peroxidase which has 4 atoms of selenium (Se) bound as seleno-cysteine moieties. During this process GSH is oxidized and is then regenerated by a reductase. Glutathione reductase is increased in the CSF of patients with MS. [Calabrese V et al., Changes in cerebrospinal fluid levels of malondialdehyde and glutathione reductase activity in multiple sclerosis. Int J Clin Pharmacol Res. 1994; 14(4): 119-23.] By contrast, low levels of glutathione peroxidase were found in MS patients. [Mai J et al., High dose antioxidant supplementation to MS patients. Effects on glutathione peroxidase, clinical safety, and absorption of selenium. Biol Trace Elem Res. 1990 Feb;24(2):109-17.] Taken together, these data suggest a disordered glutathione metabolism in MS, which accords with the evidence that oxidative stress is a part of this disease. Inherited glutathione synthetase deficiency has been described; it is accompanied by progressive peripheral and central neurological disorders. [Meister A, Larsson A. GSH synthetase deficiency and other disorders of the g-glutamyl cycle. In: Scriver CR, et al., eds. The Metabolic and Molecular Bases of Inherited Disease (Volume 1). New York: McGraw-Hill; 1995;1461-1495 (Chapter 43).]
GSH is a tripeptide composed of glutamate, cysteine and glycine. It is thought not to be absorbed intact from the gut and must be made in the body. Glutamate and glycine are well represented in the diet; cysteine less so. The concentration of this amino acid is thus the limiting factor in the synthesis of glutathione. The best form of supplementation is N-acetyl cysteine (NAC) which is safer than cysteine.
Supplementation of diet with NAC in MS patients elevates levels of GSH peroxydase. [Mai J et al., High dose antioxidant supplementation to MS patients. Effects on glutathione peroxidase, clinical safety, and absorption of selenium. Biol Trace Elem Res. 1990 Feb;24(2):109-17.] Selenium is required for the synthesis of GSH peroxydase (see above.) Selenium levels are low in patients with MS. Mai and colleagues (above) found that supplementation with selenium normalized the low levels of this element.
N-acetyl cysteine and selenium would seem to be useful supplements for restoring GSH stores; this is particularly important as GSH plays a part in the regeneration of other antioxidants.
Carnitine and acetyl L-carnitine (ALC) facilitate the transport of fatty acids across the mitochondrial membrane. The acetyl group of ALC is used in the biosynthesis of acetyl-CoA, a key intermediary in the generation of cellular energy. Depletion of ALC increases mitochondrial stress. Supplementation with ALC reduced fatigue in Chronic Fatigue Syndrome [Vermeulen RC, Scholte HR. Exploratory open label, randomized study of acetyl- and propionylcarnitine in chronic fatigue syndrome. Psychosom Med. 2004 Mar-Apr;66(2):276-82.] It also alleviated fatigue in MS. [Tomassini V et al., Comparison of the effects of acetyl L-carnitine and amantadine for the treatment of fatigue in multiple sclerosis: results of a pilot, randomised, double-blind, crossover trial. J Neurol Sci. 2004 Mar 15;218(1-2):103-8.]
Peroxynitrite is a strong oxidant capable of damaging target tissues, particularly the brain, which is known to be endowed with limited antioxidant buffering capacity. Inducible nitric oxide synthase is upregulated in the CNS in patients with MS. [Calabrese V et al., Disruption of thiol homeostasis and nitrosative stress in the cerebrospinal fluid of patients with active multiple sclerosis: evidence for a protective role of ALC. Neurochem Res. 2003 Sep;28(9):1321-8.] These authors comment: 'Western blot analysis showed in MS patients increased nitrosative stress associated with a significant decrease of reduced glutathione (GSH). Increased levels of oxidized glutathione (GSSG) and nitrosothiols were also observed. Interestingly, treatment of MS patients with ALC resulted in decreased CSF levels of NO reactive metabolites and protein nitration, as well as increased content of GSH and GSH/GSSG ratio. Our data sustain the hypothesis that nitrosative stress is a major consequence of NO produced in MS-affected CNS and implicate a possible important role for acetylcarnitine in protecting brain against nitrosative stress, which may underlie the pathogenesis of MS.'
ALC has many prophylactic properties. It was found to protect against acoustic damage to the inner ear in an animal model [Kopke R et al., Prevention of impulse noise-induced hearing loss with antioxidants. Acta Otolaryngol. 2005 Mar;125(3):235-43.]
Reviewing the literature, Ames and Liu conclude that trials of ALC in the treatment of mild cognitive impairment and mild Alzheimer's disease showed significant efficacy vs. placebo. [Ames BN, Liu J. Delaying the mitochondrial decay of aging with acetylcarnitine. Ann N Y Acad Sci. 2004 Nov;1033:108-16. Review.]
ALC treatment was found to be efficacious in alleviating symptoms, particularly pain, and improved nerve fiber regeneration and vibration perception in patients with established diabetic neuropathy. [Sima AA et al., Acetyl-L-carnitine improves pain, nerve regeneration, and vibratory perception in patients with chronic diabetic neuropathy: an analysis of two randomized placebo-controlled trials. Diabetes Care. 2005 Jan;28(1):89-94.]
In a cell culture study ALC was found to protect against damage caused by beta-amyloid (Abeta), a neurotoxic peptide which accumulates in the brain in Alzheimer's disease. [Dhitavat S, Ortiz D, Shea TB, Rivera ER. ALC protects against amyloid-beta neurotoxicity: roles of oxidative buffering and ATP levels. Neurochem Res. 2002 Jun;27(6):501-5.] These authors found that ALC attenuated oxidative stress and cell death induced by beta-amyloid neurotoxicity. They comment: 'Abeta depleted ATP levels, suggesting Abeta may induce neurotoxicity in part by compromising neuronal energy. ALC prevented ATP depletion; therefore, ALC may mediate its protective effect by buffering oxidative stress and maintaining ATP levels.' This is particularly interesting when considering chronic Chlamydia pneumoniae infection; the mechanism of accentuation of oxidative damage by ATP starvation may be similar. Electron microscopic studies have shown that replicating chlamydiae are always found in close proximity to mitochondria; they are obligate energy parasites, their metabolic function being a reversal of that of mitochondria. [reviewed by Stratton CW, The pathogenesis of systemic chlamydial infections: theoretical considerations of host-cell energy depletion and its metabolic consequences. Antimicrobics and infectious diseases newsletter. 1997; 16 (5) 33-38.]
Oxidative damage may be an important factor in neurone-loss associated with ageing. In an rat model Liu and colleagues demonstrated that oxidative damage to nucleic acids (8-hydroxyguanosine and 8-hydroxy-2'-deoxyguanosine) increased with age in the hippocampus, a region of the brain concerned with 'encoding' memory from the immediate circumstance. Oxidative damage to nucleic acids occurred predominantly in RNA. Dietary administration of ALC and / or a-lipoic acid significantly reduced the extent of oxidized RNA, the combination being the most effective. [Liu J et al., Memory loss in old rats is associated with brain mitochondrial decay and RNA/DNA oxidation: partial reversal by feeding acetyl-L-carnitine and/or R-a -lipoic acid. Proc Natl Acad Sci U S A. 2002 Feb 19;99(4):2356-61. Erratum in: Proc Natl Acad Sci U S A 2002 May 14;99(10):7184-5.]