Alternative Therapies for Multiple Sclerosis ©

By David Steenblock, M.S., D.O.

This review is for educational purposes only and is not intended to be a substitute for your physician's advice.

Antioxidants

Free radicals, including peroxynitrite are induced in Multiple Sclerosis. Antioxidants can help protect the neural tissue from damage, induced by inflammatory cascades that result in free radical pathology and oxidative stress. Nordik investigated the clinical effects of providing dietary advice, vitamin supplementation and fish oil supplementation to newly diagnosed multiple sclerosis patients. At the end of a two year period, there was a significant reduction in the mean annual exacerbation rate and the mean Expanded Disability Status Scale (EDSS) as compared to pre-study values. Plasma total phospholipid n-3 fatty acids increased and n-6 fatty acids decreased significantly (62). The cod liver oil and fish oils used should be free of heavy metals.

Antioxidants and Tissue Necrosis Factor alpha:

TNFalpha, a pro-inflammatory cytokine, has been associated with demyelinating disorders, including Multiple Sclerosis. It reduces the gene expression (PPARdelta), responsible for oligodendrocyte survival and differentiation in oligodendrocyte progenitor cells. The reduction in PPARdelta gene expression results in reductions in myelin synthesis, maturation and turnover (16). TNFalpha is inhibited by green tea, curcumin, (76), quercetin (35) and resveratrol (98).

Antioxidants and Lipopolysaccharide

The "leaky gut" syndrome allows bacterial lipopolysaccarides to enter the blood stream. Lipopolysaccharides (LPS) are associated with extensive oligodendrocyte death (47). Several natural products have the ability to protect the microglia from lipopolysaccharide-induced neurotoxicity. LPS is a component of the bacterial wall of gram-negative bacteria and is one of the most potent activators of host inflammatory response and tissue injury. LPS treatment of microglial cells activates both p38 mitogen-activated protein kinase and nuclear factor-kappaB (NFkappaB), with consequent increases in interluekin-1 alpha, tumor necrosis factor-alpha (TNF-alpha), and nitric oxide (NO) production (49). LPS also increases stress indices, including plasma corticosterone and glucose concentrations; alterations in brain oxidative status, including elevated malondialdehyde levels (a lipid peroxidation index) and decreases in reduced glutathione; and brain metabolism disturbances including reductions in ATP/ADP ratios and increases in mitochondrial/cytosolic hexokinase ratios (41).

1) Silymarin from milk thistle can reduce LPS-induced superoxide generation and nuclear factor kappaB activation (99).

2) In in vitro studies, Vitamin E (alpha-tocopherol) activates microglial activity and silences an LPS-activated NF kappa B signaling cascade. The results suggest that alpha-tocopherol can induce quiescence to pathways associated with acute or chronic inflammatory conditions in the central nervous system (21b).

3) Melatonin functions as an antioxidant and has the ability to protect neurons from lipopolysaccharide-induced oxidative stress (72).

4) N-acetylcysteine, a thiol antioxidant significantly reduces LPS-induced ROS production (superoxide anion), TNF alpha levels and NF-kappa B activity in macrophages from mice with lethal endotoxic shock. The levels approached those of macrophages from the control animals (94).

5) Estrogen and progesterone, at concentrations consistent with late pregnancy, inhibit LPS-induced nitric oxide and TNF-alpha production by activated microglia, and may contribute to the decreased severity of MS symptoms associated with pregnancy (20). Dr. Bansil and associates found a relationship between relapsing-remitting MS in 30 women and hormone fluctuations in the menstrual cycle. Those patients with a high estrogen to progesterone ratio had a significantly greater number of active MRI lesions than those with a low ratio (4). Progesterone is a known immune quieting agent.

Foods as Medicine

6) Green Tea, containing catechin and (-)-epigallocatechin-3-gallate (EGCG), has the ability to inhibit lipoplysaccharide and gamma-interferon-induced oxidative stress (3). Black tea has similar effects from inhibiting LPS-induced IkappaB kinase and NFkappaB activity (66).

7) Artichoke (102) has protective properties against inflammatory mediators, TNF alpha and LPS, in vitro.

8) Carnosol is a naturally occurring phytopolyphenol found in rosemary. Carnosol functions as an antioxidant and anticarcinogen. Carnosol significantly reduced LPS-induced nitric oxide and NF-kappa B production in a dose-dependent manner (50).

9) Quercetin (in onions and garlic) significantly inhibited LPS-induced nitric oxide production and suppressed the release of NF-kappaB (61).

10) The combination of Ginkgo biloba and quercetin were effective in inhibiting LPS-induced NF-kappa B as well as TNF-alpha activation (96).

11) Avocado contains antioxidants (persenone A and B) that can inhibit superoxide and nitric oxide generation induced by lipopolysaccharide and interferon-gamma in mouse macrophage cells (43).

12) Resveratrol in grape juice (red wine's alcoholic content can increase homocysteine levels-(7) has antioxidant and anti-inflammatory effects. Resversatrol strongly inhibits LPS-induced superoxide radical and hydrogen peroxide, arachidonic acid release, and cyclooxygenase-2 induction (54).

Alpha-Lipoic Acid

Alpha lipoic acid was administered to mice with experimental autoimmune encephalomyelitis resulting in minimal inflammation and reductions in demyelination and axonal loss in the spinal cord. Alpha lipoic acid inhibited the activity of metalloproteinase-9 in a dose-dependent manner. The authors conclude that alpha lipoic acid is highly effective at suppressing and treating experimental autoimmune encephalomyelitis and does so by inhibiting T cell trafficking into the spinal cord, perhaps by acting as a metalloproteinase inhibitor (52).

Vitamin E Succinate and all-trans-retinoic acid:

Vitamin E Succinate suppressed Epstein-Barr growth by 87% in vitro and all-trans-retinoic acid blocked Epstein-Barr activity by 58% in vitro, via transforming growth factor beta (92). Transforming Growth Factor Beta plays a role in neuronal survival and regeneration in Schwann Cell lesions (56). Vitamin E has direct neuroprotective antioxidant effects as well as anti-inflammatory indirect effects. Vitamin E inhibits microglial activation by suppressing the LPS-induced p38 MAPK and Nfkappa B signaling effects necessary for microglial activation (49).

Odinak treated 14 patients with relapsing-remitting MS with a combination of antioxidants and neuroprotectors with various mechanisms of action (lipoic acid, nicotinamide, Acetyl cysteine, Beta-carotine, alpha-tocopheryl acetate, ascorbic acid, selenium, pentoxifylline, cerebrolysin, and Amantadine hydrochloride for a duration of one month, twice a year. The treatment resulted in a significant reduction (2-3 times) of relapse frequencies in multiple sclerosis patients and a decrease of required corticosteroid medication. After antioxidant therapy the content of lipid peroxide products was significantly reduced and the author recommends antioxidant and neuroprotective program in relapsing-remitting multiple sclerosis (63).

Autoimmune Suppression

Dihydroxyvitamin D3 can either prevent or markedly suppress experimental autoimmune encephalomyelitis, rheumatoid arthritis, systemic lupus erythematosus, type I diabetes, and inflammatory bowel disease. The animals also needed to be on moderate to high calcium diets. Vitamin D hormone stimulates transforming growth factor and interleukin-4 production, which may suppress inflammatory T cell activity (19). In an animal study using the multiple sclerosis model of autoimmune encephalomyelitis, the administration of 1,25-dihydroxyvitamin D3 demonstrated rapid clinical improvement in the rats, accompanied by an inhibition of CD4, MHC class II and type II nitric oxide synthase expression (25). 1,25-dihydroxyvitamin D3 has also been reported to increase intracellular levels of glutathione, important in protecting neurons from oxidative stress-induced injury (79).

In addition, photoimmunology studies have shown that ultraviolet B can specifically attenuate autoimmune disease processes, perhaps by increasing vitamin D levels (68).

Cyclosporin A is widely used as an immunosuppressant by suppressing cytokine gene expression and inhibiting T lymphocytes. It may also protect against white matter lesions in stroke during hypoperfusion (97). However, the use of cyclophosphamide, either alone or in combination with Cyclosporin showed a significant reduction in oligodendrocyte-mediated remyelination in rat spinal cord demyelinated lesions (82).

Anti-inflammatory Diet

Vegan Diets

Quasi-vegan diets are beneficial in the management of rheumatoid arthritis, MS, and SLE (57) In his Integrative Management approach to Multiple Sclerosis, Dr. Kidd suggests a diet low in saturated fats, three fish meals per week, and the elimination of allergenic foods and products. Small frequent meals are preferable to large three meals a day. Also avoid animal fats, fried foods, sugars and sweets, and processed and refined foods.

Fresh, whole fruits, vegetables, grains, legumes, nuts and seeds include a synergy of bioavailable nutrients, enzymes, antioxidants and fiber that can retard and reverse age-related declines in cognitive and motor performance in rats (24) and can be an important component in a total lifestyle program for maximizing neuronal and cognitive function and reversing disease in humans.

Reduce Allergenic Foods

The avoidance of milk may benefit patients with MS. Peptides in milk can mimic antigens in myelin. CNS degeneration that resembles MS can be induced in mice with milk peptide injections (42).

Fatty Acids

Dietary omega-3 fatty acids can be of great benefit to MS patients. Omega-3 fatty acids have been shown to alleviate pain in autoimmune disorders by inhibiting inflammatory mediators (eicosanoids and cytokines) in peripheral tissues as well as in glial cells Omega-3 fatty acids modulate voltage-gated calcium channels in heart and brain cells, preventing electrical hyperexcitability and a cascade of events leading to cell depolarization, oxidative stress, inflammation, cell injury and pain. Omega-3 fatty acids are safe as long as they supply less than 10% of the total energy intake and are given with sufficient amounts of vitamin E (78). Cod liver oil with its vitamin A and D content (1 tablespoon 2-3 times a day) is often of great benefit to MS patients.

Lecithin

Abnormal lipid metabolism in the brain is often seen in subjects with multiple sclerosis. Lecithin cholesterol acyltransferase from the cerebrospinal fluid was investigated in 16 subjects, half control subjects and half with active demyelinating disease. The levels of lecithin cholesterol acyltransferase in patients with active demyelinating disease or multiple sclerosis was only about half of that found in the control subjects (1).

Magnesium

Magnesium, zinc and calcium have been found to be deficient in central nervous system tissue in MS patients, especially in white matter tissue (100). Magnesium is important for the metabolism of thiamine, calcium, potassium, phosphorus, iron, sodium, hydrogen chloride, acetylcholine, nitric oxide, and for many enzymes, and for the elimination of lead and cadmium. Calcium and magnesium are also important in the development, structure and stability of myelin (28). A magnesium deficiency is associated with increased inflammation. The pathologies associated with magnesium deficiency range from cardiovascular disease to cancer and include peroxynitrite damage in multiple sclerosis (37). The effects of magnesium glycerophosphate oral therapy were studied in a woman with severe spastic paraplegia resulting from MS. There was significant improvement in the spasticity after only one week of treatment. No side effects were reported (73). Natural sources of magnesium include fresh green vegetables (chlorophyll), raw wheat germ, soybeans, low fat milk, whole grains, fish, figs, corn, apples, and almonds.

Octacosanol contained in wheat germ and wheat germ oil increased endurance, total body reaction times, ECG, brachial pulse waves, pulse rate test, basal metabolism and oxygen intake tests in a physical training program with 894 subjects (18). Octacosanol is a constituent of Policosanol, now being used for cardiovascular health. Dr. Atkins was successful in treating MS patients with a low-carbohydrate diet, supplemented with vitamin B12, vitamin D3, fish oil, octacosanol, L-carnitine, coenzyme Q10, panthethine vitamin C, and calcium AEP (www.stkinscenter.com).

Digestion, Assimilation and Gut Flora

Patients with Inflammatory Bowel Disease have shown MS type lesions on the MRI, suggesting a link between gut dysbiosis and brain disorders (42).

Pancreatic enzymes

Pancreatic enzymes have been used to help reduce malabsorption and help disperse circulating immune complexes.

Anti-Candida Programs

Candida antibodies are often present in MS patients, suggesting an on-going chronic gastrointestinal yeast infection. This irritates the gut causing increased gut permeability and the subsequent absorption of glial toxic lipopolysaccharides. Transfer Factor, in conjunction with an aggressive anti-Candida program and probiotic recolonization should improve this condition.

In conclusion, there are a number of factors that can help promote stem cell proliferation and differentiation, reduce viral infections and inflammation, promote antioxidant defenses against oxidative stress and rebalance the gut flora, if needed. Test results of specific deficiencies should be used to devise rotating diets for each MS patient.

For Stem Cell Research References Click Here!