Key Clinical Studies : CerefolinNAC®

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N-acetylcysteine

1. Controlled trial of N-acetylcysteine for patients with probable Alzheimer's disease.
   Adair JC, Knoefel JE and Morgan N.
   Neurology. 2001;57:1515-1517.
2. Plasma homocysteine and thiol compound fractions after oral administration of N-acetylcysteine.
   Hultberg B, Andersson A, Masson P, Larson M and Tunek A.
   Scand.J.Clin.Lab Invest. 1994;54(6):417-22.
3. Clinical Applications of N-acetylcysteine.
   Kelly GS.
   Alternative Medicine Review 1998;3(2);114-127.
4. Co-administration of N-acetylcysteine, vitamin B₁₂ and folate in cognitively impaired hyperhomocysteinaemic patients.
   McCaddon A, Davies G.
   International Journal of Geriatric Psychiatry. 2005;20(10):998-1000.
5. Homocysteine and cognitive impairment; a case series in a General Practice setting.
   McCaddon, A.
   Nutrition Journal. 2006;5:6 [http://www.nutritionj.com/content/5/1/6]
6. Congeners of N^GAMMA-Acetyl-L-Cysteine but not Aminoguanidine act as neuroprotectants from the lipid peroxidation product 4-Hydroxy-2-Nonenal.
   Neely MD, Zimmerman L, Picklo M et.al.
   Free Radical Biology and Medicine. 2000.29(10);1028-1036.
7. Urinary and plasma homocysteine and cysteine levels during prolonged oral N-acetylcysteine therapy.
   Ventura P, Panini R, Abbati G, Marchetti G and Salvioli G.
   Pharmacology. 2003;68(2):105-14.
8. N-acetylcysteine treatment lowers plasma homocysteine but not serum lipoprotein(a) levels.
   Wiklund O, Fager G, Andersson A, Lundstam U, Masson P and Hultberg B.
   Atherosclerosis. 1996;119:99-106.

Oxidative Stress

1. Neurodegenerative diseases and oxidative stress.
   Barnham K, Masters C and Bush A.
   Nature Reviews Drug Discovery 2004;3:205-214.
2. 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.
   Boyd-Kimball D, Sultana R, Abdul HM and Butterfield DA.
   Journal of Neuroscience Research. 2005;79:700-706.
3. Oxidative imbalance in patients with mild cognitive impairment and Alzheimer's disease.
   Guidi I, Galimberti D, Lonati S, Novembrino C, Bamonti F, Tiriticco M, Fenoglio C, Venturelli E, Baron P, Bresolin N and Scarpini E.
   Neurobiology of Aging. 2006;27(2):262-269.
4. Homocysteine potentiates ß-amyloid neurotoxicity: role of oxidative stress.
   Ho P, Collins S, Dhitavat S, Ortiz D, Ashline D, Rogers E, Shea T.
   Journal of Neurochemistry. 2001;78:249-253.
5. Evidence of increased oxidative damage in subjects with mild cognitive impairment.
   Keller J, Schmitt F, Scheff S, Ding Q, Chen Q, Butterfield, D and Markesbery W.
   Neurology 2005;64:1152-1156.
6. Alzheimer's Disease and Total Plasma Aminothiols
   Andrew McCaddon, Peter Hudson, Diane Hill, Joan Barber, Alwyn Lloyd, Gareth Davies, and Björn Regland
   Biol Psychiatry 2003;53:254-260 ©2003 Society of Biological Psychiatry
7. In-vivo glutathione elevation protects against hydroxyl free radical-induced protein oxidation in rat brain
   Pocernich C, La Fontaine M, Butterfield DA.
   Neurochemistry International. 2000;36:185-191.

Homocysteine

1. Why do homocysteine levels increase?
   Bolander-Gouaille C.
   Focus on Homocysteine and the Vitamins Involved in its Metabolism, 2nd edition. Springer 2002, 69-117.
2. Homocysteine and cognitive performance in the Framingham offspring study: age is important.
   Elias MF, Sullivan LM, D'Agostino RB, et al.
   Am J Epidemiol. 2005; 162:644-653.
3. Vitamin B₁₂-B₆-folate treatment improves blood-brain barrier function in patients with hyperhomocysteinaemia and mild cognitive impairment.
   Lehmann M, Regland B, Blennow K, Gottfries CG.
   Geriatr Cogn Disord 2003; 16:145-150.
4. Neurotoxicity associated with dual actions of homocysteine at the N-methyl-D-aspartate receptor.
   Lipton SA, Kim WK, Choi Y-B, et al.
   Proceedings of the National Academy of Sciences of the USA 1997; 94:5923-5928.
5. Homocysteine and cognitive decline in healthy patients.
   McCaddon A, Hudson P, Davies G, Hughes A, Williams JHH, Wilkinson C.
   Dement Geriatr Cogn Disord. 2001; 12:309-313
6. Improvement of cognitive functions after cobalamine/folate supplementation in elderly patients with dementia and elevated plasma homocysteine.
   Nilsson K, Gustafson L, Hultberg B.
   Int J Geriatr Psychiatry 2001; 16:609-14.
7. Plasma homocysteine as a risk factor for dementia and Alzheimer's disease.
   Seshadri S, Beiser A, Selhub J, Jacques PF, Rosenberg IH, D'Agostino RB, Wilson PWF, and Wolf PA
   New England Journal of Medicine. 2002;346(7):476-483.
8. High homocysteine and low B vitamins predict cognitive decline in aging men: the Veterans Affairs normative aging study.
   Tucker KL, Qiao N, Scott T, Rosenberg I, Spiro A.
   American Journal of Clinical Nutrition. 2005; 82(3):627-635.
9. Pathogenicity of Thermolabile Methylenetetrahydrofolate Reductase for Vascular Dementia.
   Yoo J-H.
   Arterioscler Thromb Vasc Biol 2000; 20:1921-1925.

Folate Efficacy

1. Short-Term Folate, Vitamin B-12 or Vitamin B-6 Supplementation Slightly Affects Memory Performance But Not Mood in Women of Various Ages.
   Bryan J, Calvaresi E and Hughes D.
   J. Nutr. 2002;132:1345-1356.
2. Folate deficiency in elderly subjects: value of folate supplementation in the management of behavior disorders. (In French)
   Brocker P, Lebel C, Maurin H, Lods JC.
   Sem Hôp Paris. 1986;62(27):2135-2139.
3. Reduced risk of Alzheimer's disease with high folate intake: The Baltimore Longitudinal Study of Aging.
   Corrada M, Kawas C, Halldrisch J, Muller D, Brookmeyer R
   Alzheimer's & Dementia. 2005;1:11-18.
4. Effects of 3-year Folic Acid Supplementation on Cognitive Function in Older Adults in the FACIT trial: A randomized, double-blind, controlled trial.
   Durga J, van Boxtel PJ, Schouten EG, Kok FJ, Jolles J, Katan MB, Verhoef P.
   The Lancet. 2007;369:208-215.
5. Low folate levels in the cognitive decline of elderly patients and the efficacy of folate as a treatment for improving memory deficits.
   Fioravanti M, Ferrario E, Massaia M, Cappa G, Rivolta G, Grossi E and Buckley AE.
   Arch Gerontol Geriatr. 1997;26:1-13.
6. Vitamin B12-B6-Folate treatment improves Blood-Brain Barrier function in patients with Hyperhomocysteinaemia and Mild Cognitive Impairment
   Lehmann M, Regland B, Blennow K, and Gottfries CG
   Dementia and Geriatric Cognitive Disorders. 2003;16:145-150
7. Folate and vitamin B-12 status in relation to anemia, macrocytosis, and cognitive impairment in older Americans in the age of folic acid fortification.
   Morris MS, Jacques PF, Rosenberg IH, Selhub J.
   Am J Clin Nutr. 2007;85:193-200.
8. Improvement of cognitive functions after cobalamin/folate supplementation in elderly patients with dementia and elevated plasma homocysteine
   Nilsson K, Gustafson L, and Hultberg B
   International Journal of Geriatric Psychiatry. 2001;16:609-614.
9. Blood Folates Deficiencies and Cognitive Functions in Aging
   Rapin JR, Le Poncin M, Grebyl J
   In Steinhagen-Thiessen E and Knook DL, ed. Trends in Biomedical Gerontology. Vol. 1. Rijswijk, The Netherlands: TNO Institute for Experimental Gerontology; 1987:221-223.