Posted by Phillipa on January 23, 2008, at 19:03:18
In reply to Re: corr. Dopamine for ADHD » ShawnThomas, posted by SLS on January 23, 2008, at 6:36:23
Scott no flatulance for me are you switching or thinking of switching because of mood stabalizers too? Phillipa sure you've read this but her it is anyway.
Package Insert
Cerefolin®NAC Caplets
A medical food for the dietary management of neurovascular oxidative stress and/or hyperhomocysteinemia.Description
Each oval coated blue colored caplet contains:Dietary Ingredients:
L-methylfolate [6(S)-5-MTHF] (Metafolin®) 5.6 mg
Methylcobalamin 2 mg
N-acetylcysteine 600 mgOther Ingredients:
Microcrystalline Cellulose, Opadry tm Blue 07F90856 (Hypromellose, Talc, Titanium Dioxide, Polyethylene Glycol, FD&C Blue #2-Aluminum Lake, Saccharin Sodium), Magnesium Stearate (Vegetable Source).Cerefolin®NAC caplets do not contain sugar, lactose, yeast or gluten.
Indication and Usage
Cerefolin®NAC caplets are indicated for the distinct nutritional requirements of individuals under a physician's treatment for neurovascular oxidative stress6 8 9 and/or hyperhomocysteinemia;7 with particular emphasis for those individuals diagnosed with or at risk for mild to moderate cognitive impairment1 5, vascular dementia,2 4 5 Alzheimer's disease3 4 5 8 and/or recurrent or ischemic stroke.13 14Pharmacology
L-methylfolate
L-methylfolate or 6(S)-5-methyltetrahydrofolate [6(S)-5-MTHF], is the primary biologically active isomer of folate and the form of folate in circulation. It is also the form which is transported across membranes into peripheral tissues, particularly across the blood brain barrier. In the cell, 6(S)-5-MTHF is used in the methylation of homocysteine to form methionine and tetrahydrofolate (THF). THF is the immediate acceptor of one carbon units for the synthesis of thymidine-DNA, purines (RNA and DNA) and methionine. About 70% of food folate and cellular folate is comprised of 6(S)-5-MTHF. Folic acid, the synthetic form of folate, must undergo enzymatic reduction by methylenetetrahydrofolate reductase (MTHFR) to become biologically active. Genetic mutations of MTHFR result in a cell's inability to convert folic acid to 6(S)-5-MTHF.
Methylcobalamin
Methylcobalamin (Methyl-B12) is one of two forms of biologically active vitamin B12. Methyl-B12 is the principal form of circulating vitamin B12, hence the form which is transported into peripheral tissue. Methyl-B12 is absorbed by a specific intestinal mechanism which uses intrinsic factor and by a diffusion process in which approximately 1% of the ingested dose is absorbed. Cyanocobalamin and hydroxycobalamin are forms of the vitamin that require conversion to Methyl-B12 via the intermediate glutathionyl-B12.
N-acetylcysteine
N-acetylcysteine (NAC) is a precursor to glutathione (GSH) one of the body's most potent natural antioxidants. NAC is converted to GSH intracellularly. The presence of appropriate amounts of intracellular GSH helps to maintain the ability of the neurovascular tissue to metabolize vitamin B12 and to reduce or eliminate oxidative stress in these tissues. NAC significantly lowers plasma homocysteine concentrations 7 11 and increases total antioxidant capacity (TAC)12, thus correcting the characteristic pattern of changes in cognitively impaired patients with hyperhomocysteinemia 4 5 6.
Precautions
Folates, when administered as a single agent in doses above 0.1mg daily, may obscure pernicious anemia in that hematologic remission can occur while neurological manifestations remain progressive. The 2 mg of methylcobalamin contained in Cerefolin®NAC provides an adequate amount of methylcobalamin to address this possibility10. NAC should be avoided by nursing mothers. NAC clearance is reduced in those with chronic liver disease as well as in pre-term newborns. Headaches may be intensified in those taking NAC and nitrates for the treatment of angina. While the incidence of renal stones is low, those that do form renal stones, particularly cysteine stones should avoid Cerefolin®NAC. Do not administer Cerefolin®NAC to critically ill patients. NAC and its sulfhydryl metabolites could produce a false-positive result in the nitroprusside test for ketone bodies used in diabetes. Cerefolin®NAC should be used with caution in those with a history of peptic ulcer disease since NAC may disrupt the gastric mucosal barrier.Adverse Reactions
While allergic sensitization has been reported following both oral and parenteral administration of folic acid, allergic sensitization has not been reported with the use of Metafolin®. Mild transient diarrhea, polycythemia vera, itching, transitory exanthema and the feeling of swelling of the entire body have been associated with methylcobalamin. Nausea, vomiting, headache, other gastrointestinal symptoms, and rash (with or without mild fever) have been associated with NAC. There are rare reports of renal stone formation with NAC.Contraindications
Known hypersensitivity to any of the components in the product is a contraindication.Drug Interactions
Anticonvulsants (carbamazepine, fosphenytoin, phenytoin, phenobarbital, primidone valproic acid) may cause decreased serum folate levels, while high doses of folates may result in decreased serum levels of these drugs. Concomitant use of either cholestyramine, sulfasalazine, or colestipol and folate may cause decreased absorption of folate. Colchicine can depress blood folate levels. Large therapeutic doses of NSAIDS may exert antifolate activity. Phenytoin may decrease serum folate levels and negatively affect folate status. High doses of folate may cause a decrease in serum phenytoin levels. High doses of folate and pyrimethamine may cause a pharmacodynamic antagonism of the antiparasitic effect of pyrimethamine. Antibiotics may alter the intestinal microflora and may decrease the absorption of methylcobalamin. Cholestyramine, colchicines or colestipol may decrease the enterohepatic reabsorption of methylcobalamin. Metformin, para-aminosalicylic acid and potassium chloride may decrease the absorption of methylcobalamin. Nitrous oxide can produce a functional methylcobalamin deficiency. NAC along with nitrates may cause headaches. Use of NAC with carbamazepine may cause reduced serum levels of carbamazepine. Capecitabine (Xeloda®) toxicity may increase with the addition of leucovorin (5-formyltetrahydrofolate) (folate).Patient Information
Cerefolin®NAC is a medical food for use only under the direction and supervision of a licensed physician.Dosage and Administration
Usual adult dose is one caplet daily or as directed by a physician. Cerefolin®NAC is not recommended for use with children under the age of twelve.How Supplied
Available as an oval coated blue colored caplet. Debossed with "PAL" on one side and "600" on the other. Commercial product is supplied in bottles of 90 or 500 caplets. Sample product is supplied in a carton containing five blisters with one caplet in each blister.Storage
Store at controlled room temperature 15°C to 30°C (59°F to 86°F) (See USP). Protect from light and moisture. Dispense commercial product (90 caplets) in original light-resistant container. Dispense sample product in original blister.Commercial Product (90 caplets) 0525-0510-90 Rx Only
Commercial Product (500 caplets) 0525-0510-50 Rx Only
Sample Product (5 caplets) 0525-0510-05 Professional Samples - Not for sale.Patents
Some or all of the following patents may apply:U.S. Patent No. 4,940,658 U.S. Patent No. 6,207,651
U.S. Patent No. 5,563,126 U.S. Patent No. 6,254,904
U.S. Patent No. 5,795,873 U.S. Patent No. 6,297,224
U.S. Patent No. 5,997,915 U.S. Patent No. 6,528,496
U.S. Patent No. 6,011,040and other pending patent applications.
References
1 Lehmann M, Regland B, Blennow K, and Gottfries CG: Vitamin B12-B6-Folate Treatment Improves Blood-Brain Barrier Function in Patients with Hyperhomocysteinaemia and Mild Cognitive Impairment. Dementia and Geriatric Cognitive Disorders 2003;16:145-150.2 Nilsson K, Gustafson L, and Hultberg B: Improvement of cognitive functions after cobalamin/folate supplementation in elderly patients with dementia and elevated plasma homocysteine. International Journal of Geriatric Psychiatry 2001;16:609-614.
3 Seshadri S, Beiser A, Selhub J, Jacques PF, Rosenberg IH, D'Agostino RB, Wilson PWF, and Wolf PA: Plasma Homocysteine As A Risk Factor For Dementia And Alzheimer's Disease. New England Journal of Medicine 2002:Vol346, No. 7:476-483.
4 McCaddon A and Davies G: Co-administration of N-acetylcysteine, vitamin B12 and folate in cognitively impaired hyperhomocysteinaemic patients. International Journal of Geriatric Psychiatry 2005;20(10):998-1000.
5 McCaddon A and Davies G: Clinical effects of co-administering N-acetylcysteine, vitamin B12 and folate in cognitively impaired hyperhomocysteinaemic patients. Haematologica Reports 2005:1(3):49-50. Poster presentation at the 5th Homocysteine Conference in Milan, Italy June 26th - June 30th 2005.
6 Guidi I, Galimberti D, Lonati S, Novembrino C, Bamonti F, Tiriticco M, Fenoglio C, Venturelli E, Baron P, Bresolin N and Scarpini E: Oxidative imbalance in patients with mild cognitive impairment and Alzheimer's disease. Neurobiology of Aging 2006;27(2):262-269.
7 Wiklund O, Fager G, Andersson A, Lundstam U, Masson P and Hultberg B: N-acetylcysteine treatment lowers plasma homocysteine but not serum lipoprotein(a) levels. Atherosclerosis 119 (1996) 99-106.
8 Adair JC, Knoefel JE and Morgan N: Controlled trial of N-acetylcysteine for patients with probable Alzheimer's disease. Neurology 2001;57:1515-1517.
9 Boyd-Kimball D, Sultana R, Abdul HM and Butterfield DA: Gamma-Glutamylcysteine Ethyl Ester-Induced Up-Regulation of Glutathione Protects Neurons Against Aß (1-42)-Mediated Oxidative Stress and Neurotoxicity: Implications for Alzheimer's Disease. Journal of Neuroscience Research 2005;79:700-706.
10 Kuzminski AM, Del Giacco EJ, Allen RH, et al. : Effective Treatment Of Cobalamin Deficiency With Oral Cobalamin. Blood 1998; 92:1191-1198.
11 Hultberg, B., Andersson, A., Masson, P., Larson, M., and Tunek, A. Plasma Homocysteine and Thiol Compound Fractions After Oral Administration of N-acetylcysteine. Scand.J.Clin.Lab Invest 1994;54(6):417-22.
12 Ventura, P., Panini, R., Abbati, G., Marchetti, G., and Salvioli, G. Urinary and Plasma Homocysteine and Cysteine Levels During Prolonged Oral N-acetylcysteine Therapy. Pharmacology 2003;68(2):105-14.
13 Boysen, G., Brander, T., Christensen, H., Gideon, R., and Truelsen, T. Homocysteine and Risk of Recurrent Stroke. Stroke 2003;34:1258-1261.
14 Tanne, D., Haim, M., Goldbourt, U., Boyko, V., Doolman, R., Adler, Y., Brunner, D., Behar, S., and Sela, B-A. Prospective Study of Serum Homocysteine and Risk of Ischemic Stroke Among Patients With Preexisting Coronary Heart Disease. Stroke 2003;34:632-636.
Metafolin® is a registered trademark of Merck KGaA, Germany. Certain rights to Cerefolin®NAC were granted under a license from COBALZ Limited, Chester, United Kingdom, CH1 1NZ.
Manufactured For
PAMLAB, L.L.C. Covington, LA 70433
Revised 9/06
PC-
poster:Phillipa
thread:807927
URL: http://www.dr-bob.org/babble/neuro/20080114/msgs/808614.html