Inosine Synergy MS

Provides a synergistic blend of ingredients to support those who may be suffering from, or those who would like to possibly help prevent, degenerative neurological disorders, including multiple sclerosis.

Inosine is a purine ribonucleoside widely found in plants and animals. It is comprised of the purine base hypoxanthine and the sugar D-ribose. Inosine is also found as a minor nucleoside in transfer RNA and is essential for proper translation of the genetic code.

The discovery of inosine as a medical supplement began with the observation that multiple sclerosis (MS) patients have lower levels of uric acid than healthy individuals, or those with some other neurological disorders[2]. It has also been classically observed that patients who suffer from gout, a disorder characterized by elevated levels of uric acid, never get MS and that these two disorders are virtually mutually exclusive. Further investigations have confirmed that uric acid acts as a potent scavenger of the peroxynitrate-dependent radicals implicated in axonal degeneration and the formation of MS lesions[1,3].

This synergistic formula also contains lipoic acid, vitamin B12 (in the methylated form) which improves methylation and is critical for healthy nervous tissue, vitamin D3 and Ginkgo biloba. Vitamin D3 is an immune regulator and has been heavily researched for many autoimmune disorders. Ginkgo helps to prevent MS exacerbations. Alpha lipoic acid has consistently shown impressive results in a number of clinical trials for neurological disorders[5,6]. It plays many roles, including raising glutathione levels which have been shown to be low in red and white blood cells, as well as cerebrospinal fluid, of patients with MS.

Serving Size: 3 caps
Servings per container: 30
Ingredients:

• Vitamin D3 (as Cholecalciferol) 3000 IU
• Vitamin B12 (as Methylcobalamin) 500 mcg
• Inosine 1500 mg
• Alpha Lipoic Acid 300 mg
• Ginkgo (Ginkgo biloba) [standardized to contain 24% Ginkgo flavone glycosides and 6% terpene lactones] 120 mg

Recommended Use: 3 capsules twice daily until serum uric acid (UA) levels reach between 7 and 9 mg/dL, then reduce dosage to 3 capsules daily.

Other Ingredients: Microcrystalline cellulose and magnesium stearate

This product does not contain: wheat, yeast, soy, gluten, eggs, dairy, artificial colors, flavors, sugars, or preservatives.

This product should be used only under the supervision of a qualified health care professional. Since the primary mechanism of inosine therapy in degenerative neurological disorders, including MS, is to raise uric acid levels, and with the understanding that excessive levels of uric acid has been shown to increase the risk of gout and kidney stones, the use of inosine should be supervised by a qualified health care provider who can perform serial assessment of uric acid levels and adjust the dosage in each individual to maintain UA levels between 7 and 9 mg/dL and not greater. While studies generally report minimal, if any, side-effects at this level of UA, sensible precauŠtions would include a recommendation to all patients on this therapy to assure adequate fluid intake (6-8 glasses of water with fresh lemon per day minimum), a low oxylate diet, limited alcohol (especially beer), and avoidance of excessive amounts of dietary and supplemental calcium.

Inosine may have neuroprotective, cardioprotective, anti-inflammatory and immunomodulatory activities. The main mechanism of inosine?s neuroprotective effect appears to be the fact that it raises levels of uric acid (UA), a peroxynitrate scavenging antioxidant1. Peroxynitrate has been implicated in the pathogenesis of various degenerative neurological disorders including MS. Inosine has been proposed for oral administration after stroke due to observation that it may encourage axonal re-wiring. Inosine has also been reported to have positive inotropic effects and to have mild vasodilation activity.

It has long been observed that multiple sclerosis (MS) patients have lower levels of uric acid than healthy individuals, or those with some other neurological disorders2. It has also been classically observed that patients who suffer from gout, a disorder characterized by elevated levels of uric acid, do not contract MS and that these two disorders are virtually mutually exclusive. Further investigations have confirmed that uric acid acts as a potent scavenger of the peroxynitrate-dependent radicals implicated in axonal degeneration and the formation of MS lesions1,3. There has also been interest in uric acid levels and inosine in degenerative neurological diseases such as Parkinson?s disease. Uric acid given orally is bacterially degraded in the gut and does not result in any appreciable increase in serum UA levels. However, oral administration of inosine can effectively increase serum uric acid levels to between 7 and 9 mg/dL, the range shown to produce positive clinical results, including reductions in frequency and duration of exacerbations in patients suffering from MS3,4. In fact, Spitsin et al reported that uric acid could be maintained at this level for a year and more without reported side effects by the oral administration of its precursor inosine1. This group also reported in several MS subjects that gadolinium-enhanced lesions observed before the administration of inosine could no longer be detected after 10-15 months of treatment.

Alpha Lipoic Acid Alpha lipoic acid (ALA) is a broad-spectrum antioxidant exhibiting protective properties for both water and lipid-based tissues. ALA also acts as an orally effective repleter of reduced glutathione (GSH). The enzyme glutathione peroxidase (GP), which detoxifies peroxides, is markedly reduced in the red blood cells, white blood cells and the CSF of MS patients. The GP enzyme system has an absolute requirement for reduced glutathione (GSH) as its substrate cofactor. Through these mechanisms, as well as its ability to act at the mitochondrial level as a Kreb?s cycle cofactor, ALA has consistently shown impressive results in a number of clinical trials for neurological disorders5,6. It has also recently been demonstrated to inhibit human T-cell migration in MS subjects7. Perlmutter, et al, have shown the successful clinical use of oral GSH repleters in Parkinson?s, Alzheimer?s, stroke, and MS8.

Vitamin D3 The availability of vitamin D decreases with increasing latitude in patterns closely correlated with increasing MS rates, and individuals with a high exposure to sunlight have a significantly lower risk of MS, independent of country of origin, age, sex, race, and socioeconomic status. In fact, the higher latitudes in both hemispheres have up to 10 times the rate of MS. MS is understood to be a disorder exhibiting underlying autoimmunity, while vitamin D has emerged as one of the most important immune regulators9. Studies have also consistently associated low levels of vitamin D with MS subjects. The relationship between vitamin D and MS remains not fully understood, and this relationship may ultimately turn out to be geographically circumstantial. While the use of vitamin D in MS and other autoimmune diseases has its detractors (Marshall, Waterhouse, et al10), the vast majority of vitamin D and MS researchers presently support the use of vitamin D, with its positive immunoregulatory properties, in MS11,12. In fact, recently researchers have found evidence that a direct interaction between vitamin D and a common genetic variant alters the risk of developing multiple sclerosis (MS). This research suggests that vitamin D deficiency during pregnancy and in early age may increase the risk of the offspring developing MS later in life13.

Ginkgo biloba Ginkgo-based flavonoids may act as effective free-radical scavengers supporting both general antioxidant defense and capillary integrity in the central nervous system. A specific component of the herb, ginkgolide B, is a particularly potent inhibitor of platelet-activating factor, a significant inflammatory mediator. While one very short duration placebo-controlled trial failed to show significant benefits in reducing acute MS exacerbations, other studies of longer-term use of ginkgo in MS patients have shown significant improvements in various outcome measures, including fatigue, general symptom severity and functionality with no adverse events14.

Vitamin B12 Vitamin B12 (methylcobalamin) has long been understood to be critical in the health of the nervous tissue15. From the very first phases of the development of the nervous system in the womb, vitamin B12 plays a critical role in proper cell differentiation by acting as a methylation cofactor. MS subjects have been shown to demonstrate poor methylation capacity, decreased levels of B12, elevated homocysteine, and resulting depression at a higher prevalence than controls16. Vitamin B12 continues to play various roles in the developed nervous tissue and has long been used successfully in the maintenance of healthy central and peripheral nervous tissue in a multitude of neurological conditions17.

1. Inactivation of peroxynitrite in multiple sclerosis patients after oral administration of inosine may suggest possible approaches to therapy of the disease. Spitsin S, Hooper DC, Leist T, et al. Mult Scler. 2001 Oct;7(5):313-9.

2. Serum uric acid and multiple sclerosis. Rentzos M, Nikolaou C, Anagnostouli M, et al. Clin Neurol Neurosurg. 2006 Sep;108(6):527-31. Epub 2005 Oct 3..

3. The treatment of multiple sclerosis with inosine. Markowitz CE, Spitsin S, Zimmerman V, et al. J Altern Complement Med. 2009 Jun;15(6):619-25.PMID: 19425822.

4. The treatment of multiple sclerosis with inosine. Whitmarsh TE. J Altern Complement Med. 2009 Jun;15(6):609..

5. The sensory symptoms of diabetic polyneuropathy are improved with alpha-lipoic acid: the SYDNEY trial. Ametov AS, Barinov A, Dyck PJ, et al. Diabetes Care. 2003 Mar;26(3):770-6..

6. Treatment of symptomatic diabetic polyneuropathy with the antioxidant alpha-lipoic acid: a 7-month multicenter randomized controlled trial (ALADIN III Study). ALADIN III Study Group. Alpha-Lipoic Acid in Diabetic Neuropathy. Ziegler D, Hanefeld M, Ruhnau KJ, et al. Diabetes Care. 1999 Aug;22(8):1296-301..

7. Alpha lipoic acid inhibits human T-cell migration: implications for multiple sclerosis. Marracci GH, McKeon GP, Marquardt WE, et al. J Neurosci Res. 2004 Nov 1;78(3):362-70..

8. Randomized, double-blind, pilot evaluation of intravenous glutathione in Parkinson's disease. Hauser RA, Lyons KE, McClain T, et al. Mov Disord. 2009 May 15;24(7):979-83..

9. Ultraviolet radiation and autoimmune disease: insights from epidemiological research. Ponsonby AL, McMichael A, van der Mei I. Toxicology. 2002 Dec 27;181-182:71-8..

10. Vitamin D Metabolism in Chronic Disease. Waterhouse JC, Marshall TG, Fenter B, Mangin M, Blaney G. In Vitamin D: New Research, Nova Science Publishers, NY, 2006..

11. Benefits and requirements of vitamin D for optimal health: a review. Grant WB, Holick MF. Altern Med Rev. 2005 Jun;10(2):94-111..

12. Examining the evidence: complementary adjunctive therapies for multiple sclerosis. Namaka M, Crook A, Doupe A, et al. Neurol Res. 2008 Sep;30(7):710-9..

13. Expression of the multiple sclerosis-associated MHC class II Allele HLA-DRB1*1501 is regulated by vitamin D. Ramagopalan SV, Maugeri NJ, Handunnetthi L, et al. PLoS Genet. 2009 Feb;5(2):e1000369..

14. The effect of Ginkgo biloba on functional measures in multiple sclerosis: a pilot randomized controlled trial. Johnson SK, Diamond BJ, Rausch S, et al. Explore (NY). 2006 Jan;2(1):19-24..

15. The multi-faceted basis of vitamin B12 (cobalamin) neurotrophism in adult central nervous system: Lessons learned from its deficiency. Scalabrino G. Prog Neurobiol. 2009 Jul;88(3):203-20..

16. Serum vitamin B12, folate, and homocysteine levels and their association with clinical and electrophysiological parameters in multiple sclerosis. Kocer B, Engur S, Ak F, Yilmaz M. J Clin Neurosci. 2009 Mar;16(3):399-403..

17. Oral cyanocobalamin supplementation in older people with vitamin B12 deficiency: a dose-finding trial. Eussen SJ, de Groot LC, Clarke R, et al. Arch Intern Med. 2005 May 23;165(10):1167-72..