BriteAge Library
The first step to improving ones cognitive performance is learning about your own brain health. BriteAge offers this library to offer a broader background of issues surrounding your brain's abilities, the issues that threaten it, and the natural supplements that aid brain function.
Natural Supplements
Choose from the list below for a complete list of references for each brain healthy natural supplement:
Ceretrophin® (proprietary blend of the following 6 natural supplements in BriteSMART®)
Biotin is a member of the B-vitamin family, is an essential nutrient in human nutrition. It is involved in the biosynthesis of fatty acids, gluconeogenesis, energy production, and the metabolism of the branched-chain amino acids (L-leucine, L-isoleucine, L-valine). Biotin improves glucose tolerance and decreases insulin resistance, both healthy factors for the brain. Biotin levels may be depleted by alpha lipoic acid intake, and therefore has been added to replenish this possible depletion, as well as boost glucose metabolism and balance.
Janos Zempleni, Timothy A. Trusty, and Donald M. Mock. Lipoic Acid Reduces the Activities of Biotin-Dependent Carboxylases in Rat Liver. The Journal of Nutrition Vol. 127 No. 9 September 1997, pp. 1776-1781.
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Sone H, Ito M, Sugiyama K, Ohneda M, Maebashi M, Furukawa Y. Biotin enhances glucose-stimulated insulin secretion in the isolated perfused pancreas of the rat. J Nutr Biochem. 1999 Apr;10(4):237-43.
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Reddi A, DeAngelis B, Frank O, Lasker N, Baker H. Biotin supplementation improves glucose and insulin tolerances in genetically diabetic KK mice. Life Sci. 1988;42(13):1323-30.
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Acetyl-L-Carnitine (ALC) is perhaps the one true miracle molecule, especially for your brain (and heart). ALC is naturally found in the brain and body. Its main dietary source is red meat, although you’d have to eat over 50lbs. a day to get enough for improved mental performance. ALC has multiple roles in the protection, preservation and performance of your brain cells. It increases brain blood flow as well as the synthesis and utilization of acetylcholine (ACh), a key neurotransmitter for mental clarity, memory and focus. It improves the energy output of your mitochondria, helps stabilize the neural membrane, and protects both from free radical damage. ALC has been shown to protect the brain even after a head injury or stroke, and it helps accelerate the healing of damaged neurons. It’s believed to help remove a serious brain damaging plaque, a dark pigment called lipofuscin. ALC also increases levels of glutathione, perhaps the brain’s most important anti-oxidant. ALC has also been shown to increase levels of nerve growth factor thus stimulating the growth of new neurons, synapses and their interconnecting “wires”, called axons and dendrites. In fact, ALC appears to rejuvenate the brain and, especially when combined with alpha lipoic acid (see below) it may significantly slow brain aging, especially in the mitochondria. And, it helps protect the brain and liver from the harmful by-products of alcohol.
Dozens of clinical studies have demonstrated ALC’s powerful effect on improving mental clarity, focus and memory, in reducing depression, and boosting processing speed and cognitive function, in both normal and cognitively impaired individuals.
Liu, Jiankang : Killilea, David W : Ames, Bruce N. Age-associated mitochondrial oxidative decay: improvement of carnitine acetyltransferase substrate-binding affinity and activity in brain by feeding old rats acetyl-L- carnitine and/or R-alpha -lipoic acid. Proc-Natl-Acad-Sci-U-S-A. 2002 Feb 19; 99(4): 1876-81.
Liu, Jiankang : Head, Elizabeth : Gharib, Afshin M : Yuan, Wenjun : Ingersoll, Russell T : Hagen, Tory M : Cotman, Carl W : Ames, Bruce N. 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-alpha -lipoic acid. Proc-Natl-Acad-Sci-U-S-A. 2002 Feb 19; 99(4): 2356-61.
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Bruno G; Scaccianoce S; Bonamini M; Patacchioli FR; Cesarino F; Grassini P; Sorrentino E; Angelucci L; Lenzi GL. Acetyl-L-carnitine in Alzheimer disease: a short-term study on CSF neurotransmitters and neuropeptides. Alzheimer Dis Assoc Disord (U.S.) Fall 1995, 9 (3) p128-31.
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Pettegrew JW; Klunk WE; Panchalingam K; Kanfer JN; McClure RJ Clinical and neurochemical effects of acetyl-L-carnitine in Alzheimer's disease. Neurobiol Aging (UNITED STATES) Jan-Feb 1995, 16 (1) p1-4.
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Forloni G; Angeretti N; Smiroldo S. Neuroprotective activity of acetyl-L-carnitine: studies in vitro. J Neurosci Res (UNITED STATES) Jan 1994, 37 (1) p92-6.
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MK Shigenaga, TM Hagen and BN Ames. Oxidative damage and mitochondrial decay in aging. Proceedings of the National Academy of Sciences, 1194, Vol 91, 10771-10778.
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Cipolli C, Chiari G. Effects of L-acetylcarnitine on mental deterioration in the aged: initial results. Clin Ter. 1990 Mar 31;132(6 Suppl):479-510.
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Pettegrew J.W.; Klunk W.E.; Panchalingam K.; Kanfer J.N.; McClure. Clinical and neurochemical effects of acetyl-L-carnitine in Alzheimer's disease. R.J.NEUROBIOL. AGING ( USA), 1995, 16/1 (1-4).
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RP Friedland, RC Petersen, JW Pettegrew, E Pfeiffer, MA Raskind, M Sano, MH Tuszynski and RF Woolson. A 1-year multicenter placebo-controlled study of acetyl-L-carnitine in patients with Alzheimer's disease LJ Thal, A Carta, WR Clarke, SH Ferris,. Neurology ( USA), 1996, 47/3 (705-711).
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Ramacci MT, Taglialatela G. Effects of acetyl-L-carnitine treatment and stress exposure on the nerve growth factor receptor (p75NGFR) mRNA level in the central nervous system of aged rats. Foreman PJ, Perez-Polo JR, Angelucci L, Prog Neuropsychopharmacol Biol Psychiatry (ENGLAND) Jan 1995, 19 (1) p117-33.
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Taglialatela G, Navarra D, Cruciani R, Ramacci MT, Alema GS, Angelucci L. Acetyl-L-carnitine treatment increases nerve growth factor levels and choline acetyltransferase activity in the central nervous system of aged rats. Exp Gerontol ( ENGLAND) Jan-Feb 1994, 29 (1) p55-66.
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Taglialatela G, Angelucci L, Ramacci MT, Werrbach-Perez K, Jackson GR, Perez-Polo JR. Stimulation of nerve growth factor receptors in PC12 by acetyl-L-carnitine. Biochem Pharmacol (ENGLAND) Aug 4 1992, 44 (3) p577-85.
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De Simone R, Ramacci MT, Aloe L.Effect of acetyl-L-carnitine on forebrain cholinergic neurons of developing rats. Int J Dev Neurosci (ENGLAND) 1991, 9 (1) p39-46
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L. Angelucci, M. T. Ramacci, G. Taglialatela, C. Hulsebosch, B. Morgan, K. Werrbach-Perez, J. R. Perez-Polo.Nerve growth factor binding in aged rat central nervous system: effect of acetyl-L-carnitine. J Neurosci Res (UNITED STATES) Aug 1988, 20 (4) p491-6.
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Dr. G. Forloni, N. Angeretti, S. Smiroldo.Neuroprotective activity of acetyl-L-carnitine: Studies in vitro.NEUROSCI. RES. ( USA), 1994, 37/1 (92-96).
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A. Carta, M. Calvani, D. Bravi and S. N. Bhuachalla.Acetyl-L-carnitine and Alzheimer's disease: Pharmacological beyond the cholinergic sphere.ANN. NEW YORK ACAD. SCI. ( USA), 1993, 695/- (324-326).
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R-Alpha Lipoic Acid (R-ALA) is the R form of ALA, and is believed to be (perhaps significantly) more biologically active than the S form. Normal alpha lipoic acid ( ALA) is racemic meaning it contains 50% the R form and 50% the S form. R-ALA is a powerful antioxidant at the mitochondrial level where its ability to tame the fires and free radicals of the oxidative, energy generating process is highly essential to protect the mitochondria from burn out. ALA revitalizes, or recycles other neuro-protective, anti-oxidant agents, such as Vitamins C and E, and CoQ10. It increases brain levels of glutathione, an important antioxidant, brain protector and immune system booster. ALA also improves blood sugar balance, lowers insulin resistance, and reduces the glycation of proteins, or AGE plaque formation. It has been shown to improve memory and actually reverse neuropathy. ALA, when combined with acetyl-l-carnitine has shown remarkable synergistic effects in slowing down brain aging at the mitochondrial level.
Thirunavukkarasu V, Anitha Nandhini AT, Anuradha CV. Lipoic acid improves glucose utilisation and prevents protein glycation and AGE formation. Pharmazie. October 2005, Vol. 60, Issue: 10, Page(s): 772-775.
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Thirunavukkarasu,-V; Anitha-Nandhini,-A-T; Anuradha,-C-V. Lipoic acid attenuates hypertension and improves insulin sensitivity, kallikrein activity and nitrite levels in high fructose-fed rats. J-Comp-Physiol-[B]. 2004 Nov; 174(8): 587-92.
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Midaoui,-A-E; Elimadi,-A; Wu,-L; Haddad,-P-S; de-Champlain,-J. Lipoic acid prevents hypertension, hyperglycemia, and the increase in heart mitochondrial superoxide production. Am-J-Hypertens. 2003 Mar; 16(3): 173-9.
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Farr, S A : Poon, H F : Dogrukol Ak, D : Drake, J : Banks, W A : Eyerman, E : Butterfield, D A : Morley, J E. The antioxidants alpha-lipoic acid and N-acetylcysteine reverse memory impairment and brain oxidative stress in aged SAMP8 mice. J-Neurochem. 2003 Mar; 84(5): 1173-83.
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Liu, Jiankang : Killilea, David W : Ames, Bruce N. Age-associated mitochondrial oxidative decay: improvement of carnitine acetyltransferase substrate-binding affinity and activity in brain by feeding old rats acetyl-L- carnitine and/or R-alpha -lipoic acid. Proc-Natl-Acad-Sci-U-S-A. 2002 Feb 19; 99(4): 1876-8.
(See Details)
Liu, Jiankang : Head, Elizabeth : Gharib, Afshin M : Yuan, Wenjun : Ingersoll, Russell T : Hagen, Tory M : Cotman, Carl W : Ames, Bruce N. 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-alpha -lipoic acid. Proc-Natl-Acad-Sci-U-S-A. 2002 Feb 19; 99(4): 2356-61.
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Arivazhagan, P : Shila, S : Kumaran, S : Panneerselvam, C. Effect of DL-alpha-lipoic acid on the status of lipid peroxidation and antioxidant enzymes in various brain regions of aged rats. Exp-Gerontol. 2002 Jun; 37(6): 803-11.
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Pirlich, M : Kiok, K : Sandig, G : Lochs, H : Grune, T. Alpha-lipoic acid prevents ethanol-induced protein oxidation in mouse hippocampal HT22 cells. Neurosci-Lett. 2002 Aug 9; 328(2): 93-6.
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Flier, J : Van Muiswinkel, F L : Jongenelen, C A : Drukarch, B. The neuroprotective antioxidant alpha-lipoic acid induces detoxication enzymes in cultured astroglial cells. Free-Radic-Res. 2002 Jun; 36(6): 695-9.
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Arivazhagan, P : Ramanathan, K : Panneerselvam, C. Effect of DL-alpha-lipoic acid on glutathione metabolic enzymes in aged rats. Exp-Gerontol. 2001 Dec; 37(1):81-7.
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Zhang, L : Xing, G Q : Barker, J L : Chang, Y : Maric, D : Ma, W : Li, B S : Rubinow, D R. Alpha-lipoic acid protects rat cortical neurons against cell death induced by amyloid and hydrogen peroxide through the Akt signalling pathway. Neurosci-Lett. 2001 Oct 26; 312(3): 125-8.
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Arivazhagan, P : Ramanathan, K : Panneerselvam, C. Effect of DL-alpha-lipoic acid on mitochondrial enzymes in aged rats. Chem-Biol-Interact. 2001 Nov 28; 138(2): 189-98.
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Rhodiola (RHO) is an herbal supplement that appears to buffer the brain against the negative effects of stress (cortisol) and other environmanetal, physical and biochemical stressors such as, work fatigue. RHO is especially effective in improving mental and physical mental performance in demanding situations. Once revealed as the secret behind the phenomenal strength and endurance feats of Bulgarian and Russian Olympic athletes, this high-altitude mountain plant is popular as an adaptogenic agent, specifically during times of stress or high-energy mental and physical performance demands. Actual studies in Europe have shown that it improved mental performance in medical students and pilots under stress. RHO increases several neurotransmitters including dopamine, which regulates focus (attention) and moods, and norepenephrine, which regulates alertness and long term memory formation.
Abidov,M; Grachev,S; Seifulla,RD; Ziegenfuss,TN. Extract of Rhodiola rosea radix reduces the level of C-reactive protein and creatinine kinase in the blood. Bull-Exp-Biol-Med. 2004 Jul; 138(1): 63-4.
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Darbinyan, V., Kteyan, A., Panossian, A., Gabrielian, E., Wikman, G., Wagner, H. Rhodiola rosea in stress induced fatigue-a double blind cross-over study of a standardized extract SHR-5 with a repeated low-dose regimen on the mental performance of healthy physicians during night duty. Phytomedicine, 2000, 7(5), 365-71.
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Spasov, A.A, Wikman, G.K, Mandrikov, V.B., Mironova, I.A. & Neumoin, V.V. A double-blind, placebo-controlled pilot study of the stimulating and adaptogenic effect of Rhodiola rosea SHR-5 extract on the fatigue of students caused by stress during an examination period with a repeated low-dose regimen. Phytomedicine, 2000, 7, 85-89.
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Shevtsov,-V-A; Zholus,-B-I; Shervarly,-V-I; Vol'skij,-V-B; Korovin,-Y-P; Khristich,-M-P; Roslyakova,-N-A; Wikman. A randomized trial of two different doses of a SHR-5 Rhodiola rosea extract versus placebo and control of capacity for mental work. G. Phytomedicine. 2003 Mar; 10(2-3): 95-105.
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De-Sanctis,R; De-Bellis,R; Scesa,C; Mancini,U; Cucchiarini,L; Dacha,M. In vitro protective effect of Rhodiola rosea extract against hypochlorous acid-induced oxidative damage in human erythrocytes. Biofactors. 2004; 20(3): 147-59.
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Germano C, Ramazanov Z, Bernal Suarez M. Arctic Root (Rhodiola Rosea):The Powerful New Ginseng Alternative. New York, NY: Kensington Publishing Corp; 1999.
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Maslova, L.V., Kondrat'ev BIu, Maslov, L.N. & Lishmanov IuB. (1994). The cardioprotective and antiadrenergic activity of an extract of Rhodiola rosea in stress. Eksperimental'naia i klinicheskaia farmakologiia, 57(6), 61-63.
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Petkov, V.D., Yonkov, D., Mosharoff A., Kambourova, T., Alova, L., Petkov, V.V. & Todorov, I. (1986). Effects of alcohol aqueous extract from Rhodiola rosea L. roots on learning and memory. Acta physiologica et pharmacologica Bulgarica, 12(1), 3-16.
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Vinpocetine (VIN) is a natural extract of the beautiful periwinkle flower, vinca minor. It increases cerebral vascular blood flow, thus enhancing the flow of nutrients, oxygen, glucose and neurotransmitter substrates, e.g., choline to the brain. VIN has been shown to improve memory and brain processing speed. It also increases brain glucose metabolism and increases the mitochondria’s generation ATP, which improves brain energy as well as mood, memory and other mental functions. It is also a powerful anti-oxidant, and neuro-protective agent that has been shown to protect brain cells against the chronic age-related reduction in oxygen levels and the acute and sudden loss of oxygen, such as after a stroke. VIN also protects the brain from imbalances in calcium regulation, or calcium overload which is another major cause of cognitive decline and brain dysfunction with age.
Subhan Z, Hindmarch H. Psychopharmacological effects of vinpocetine in normal healthy volunteers. European Journal of Clinical Pharmacology, 1985, Sept;28(5):567-571.
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DeNoble VJ, Repetti SJ, Gelpke LW, Wood LM, Keim KL. Vinpocetine: nootropic effects on scopolamine-induced and hypoxia-induced retrieval deficits of a step-through passive avoidance response in rats. Pharmacol Biochem Behav. 1986 Apr;24(4):1123-8. (
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Polich J, Gloria R. Cognitive effects of a Ginkgo biloba/vinpocetine compound in normal adults: systematic assessment of perception, attention and memory. Human Psychopharmacology:Clinical and Experimental. 1991;16(5):409-416.
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Coleston D, Hindmarch I. Possible memory-enhancing properties of vinpocetine. Drug Development Research 2004 Oct; 14(3-4):191-193.
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Balestreri R, Fontana L, Astengo F. A double-blind placebo controlled evaluation of the safety and efficacy of vinpocetine in the treatment of patients with chronic vascular senile cerebral dysfunction. J Am Geriatr Soc. 1987 May;35(5):425-30.
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Hadjiev D. Asymptomatic ischemic cerebrovascular disorders and neuroprotection with vinpocetine. The asymptomatic ischemic cerebrovascular disorders (AICVD) is an early manifestation of cerebrovascular disease. Ideggyogy Sz. 2003; 56(5-6):166-72.
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Nicholson CD. Pharmacology of nootropics and metabolically active compounds in relation to their use in dementia. Psychopharmacology (Berl). 1990; 101(2):147-59.
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Lendvai B, Zelles T, Rozsa B, Vizi ES. A vinca alkaloid enhances morphological dynamics of dendritic spines of neocortical layer 2/3 pyramidal cells. Brain Res Bull. 2003 Jan 15;59(4):257-60 .
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Horvath, Beata : Marton, Zsolt : Halmosi, Robert : Alexy, Tamas : Szapary, Laszlo : Vekasi, Judit : Biro, Zsolt : Habon, Tamas : Kesmarky, Gabor : Toth, Kalman. In vitro antioxidant properties of pentoxifylline, piracetam, and vinpocetine. Clin-Neuropharmacol. 2002 Jan-Feb; 25(1): 37-42 .
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Zelles, T : Franklin, L : Koncz, I : Lendvai, B : Zsilla, G. The nootropic drug vinpocetine inhibits veratridine-induced [Ca2+]i increase in rat hippocampal CA1 pyramidal cells. Neurochem-Res. 2001 Sep; 26(8-9): 1095-100.
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Pereira, C : Agostinho, P : Oliveira, CR. Vinpocetine attenuates the metabolic dysfunction induced by amyloid beta-peptides in PC12 cells. Free-Radic-Res. 2000 Nov; 33(5): 497-506.
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Santos , M S : Duarte, A I : Moreira, P I : Oliveira, C R. Synaptosomal response to oxidative stress: effect of vinpocetine. Free-Radic-Res. 2000 Jan; 32(1): 57-66.
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Tretter, L : Adam Vizi, V. The neuroprotective drug vinpocetine prevents veratridine-induced [Na+]i and [Ca2+]i rise in synaptosomes. Neuroreport. 1998 Jun 1; 9(8): 1849-53.
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Hayakawa, M. Comparative efficacy of vinpocetine, pentoxifylline and nicergoline on red blood cell deformability. Arzneimittelforschung. 1992 Feb; 42(2): 108-10.
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Hayakawa, M. Effect of vinpocetine on red blood cell deformability in stroke patients. Arzneimittelforschung. 1992 Apr; 42(4): 425-7.
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Kiss, B : Cai, N S : Erdo, S L. Vinpocetine preferentially antagonizes quisqualate/AMPA receptor responses: evidence from release and ligand binding studies. Eur-J-Pharmacol. 1991 Dec 10; 209(1-2): 109-12.
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Rischke, R : Krieglstein, J. Protective effect of vinpocetine against brain damage caused by ischemia. Jpn-J-Pharmacol. 1991 Jul; 56(3): 349-56.
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Hitzenberger, G : Sommer, W : Grandt, R. Influence of vinpocetine on warfarin-induced inhibition of coagulation. Int-J-Clin-Pharmacol-Ther-Toxicol. 1990 Aug; 28(8): 323-8.
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Tohgi, H : Sasaki, K : Chiba, K : Nozaki, Y.Effect of vinpocetine on oxygen release of hemoglobin and erythrocyte organic polyphosphate concentrations in patients with vascular dementia of the Binswanger type. Arzneimittelforschung. 1990 Jun; 40(6): 640-3.
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Yasui, M : Yano, I : Ota, K : Oshima, A. Calcium, phosphorus and aluminium concentrations in the central nervous system, liver and kidney of rabbits with experimental atherosclerosis: preventive effects of vinpocetine on the deposition of these elements. J-Int-Med-Res. 1990 Mar-Apr; 18(2): 142-52.
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Gaal, L : Molnar, P. Effect of vinpocetine on noradrenergic neurons in rat locus coeruleus. Eur-J-Pharmacol. 1990 Oct 23; 187(3): 537-9.
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Bonoczk, Peter : Panczel, Gyula : Nagy, Zolta. Vinpocetine increases cerebral blood flow and oxygenation in stroke patients: a near infrared spectroscopy and transcranial Doppler study. Eur-J-Ultrasound. 2002 Jun; 15(1-2): 85-91.
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Yasui M; Yano I; Ota K; Oshima A. Contents of calcium, phosphorus and aluminum in central nervous system, liver and kidney of rabbits with experimental atherosclerosis--scavenger effects of vinpocetine on the deposition of elements. No To Shinkei. 1990; 42(4):325-31.
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Gabryel, B : Adamek, M : Pudelko, A : Malecki, A : Trzeciak, H I.Piracetam and vinpocetine exert cytoprotective activity and prevent apoptosis of astrocytes in vitro in hypoxia and reoxygenation. Neurotoxicology. 2002 May; 23(1): 19-31.
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Huperzine A (HUP) is derived from Chinese Club Moss (Huperia serrata). It’s a natural acetylcholinesterase (AChE) inhibitor. AChE is the enzyme that destroys acetylcholine in the synapse before it’s effectively used to communicate your thoughts, feelings and memories. HUP helps keep your acetylcholine levels up, so your synapses fire fast and efficiently. HUP has been shown to improve memory, protect brain cells both from free radical and glutamate “excitotoxicity”, a highly damaging condition found in accelerated brain aging and Alzheimer’s. HUP also stimulates the acetylcholine receptors making them more sensitive to existing levels of ACh. HUP may also act as a brain metabolic enhancer.
Sun, Q Q : Xu, S S : Pan, J L : Guo, H M : Cao, WQ. Huperzine-A capsules enhance memory and learning performance in 34 pairs of matched adolescent students. Zhongguo-Yao-Li-Xue-Bao. 1999 Jul; 20(7): 601-3 "
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Zangara,A. The psychopharmacology of huperzine A: an alkaloid with cognitive enhancing and neuroprotective properties of interest in the treatment of Alzheimer's disease. Pharmacol-Biochem-Behav. 2003 Jun; 75(3): 675-86
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Jiang,H; Luo,X; Bai,D. Progress in clinical, pharmacological, chemical and structural biological studies of huperzine A: a drug of traditional chinese medicine origin for the treatment of Alzheimer's disease. Curr-Med-Chem. 2003 Nov; 10(21): 2231-52
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Xiao, Xiao Qiu : Zhang, Hai Yan : Tang, Xi Can.Huperzine A attenuates amyloid beta-peptide fragment 25-35-induced apoptosis in rat cortical neurons via inhibiting reactive oxygen species formation and caspase-3 activation. J-Neurosci-Res. 2002 Jan 1; 67(1): 30-6
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Zhou, J : Fu, Y : Tang, X C. Huperzine A and donepezil protect rat pheochromocytoma cells against oxygen-glucose deprivation. Neurosci-Lett. 2001 Jun 22; 306(1-2): 53-6
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Zhou, J : Zhang, H Y : Tang, X C. Huperzine A attenuates cognitive deficits and hippocampal neuronal damage after transient global ischemia in gerbils. Neurosci-Lett. 2001 Nov 9; 313(3): 137-40
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Gordon, R K : Nigam, S V : Weitz, J A : Dave, J R : Doctor, B P : Ved, H S. The NMDA receptor ion channel: a site for binding of Huperzine A. J-Appl-Toxicol. 2001 Dec; 21 Suppl 1: S47-51
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Wang, R : Zhang, H Y : Tang, X C. Huperzine A attenuates cognitive dysfunction and neuronal degeneration caused by beta-amyloid protein-(1-40) in rat. Eur-J-Pharmacol. 2001 Jun 15; 421(3): 149-56
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Wang, R : Xiao, X Q : Tang, X C. Huperzine A attenuates hydrogen peroxide-induced apoptosis by regulating expression of apoptosis-related genes in rat PC12 cells. Neuroreport. 2001 Aug 28; 12(12): 2629-34
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Wang, L M : Han, Y F : Tang, X C. Huperzine A improves cognitive deficits caused by chronic cerebral hypoperfusion in rats. Eur-J-Pharmacol. 2000 Jun 9; 398(1): 65-72
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Shang, Y Z : Ye, J W : Tang, X C. Improving effects of huperzine A on abnormal lipid peroxidation and superoxide dismutase in aged rats. Zhongguo-Yao-Li-Xue-Bao. 1999 Sep; 20(9): 824-8
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Zhao, H W : Li, X Y. Ginkgolide A, B, and huperzine A inhibit nitric oxide production from rat C6 and human BT325 glioma cells. Zhongguo-Yao-Li-Xue-Bao. 1999 Oct; 20(10): 941-3
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Xu, S S : Cai, Z Y : Qu, Z W : Yang, R M : Cai, Y L : Wang, G Q : Su, X Q : Zhong, X S : Cheng, R Y : Xu, W A : Li, J X : Feng, B. Huperzine-A in capsules and tablets for treating patients with Alzheimer disease. Zhongguo-Yao-Li-Xue-Bao. 1999 Jun; 20(6): 486-90
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Wang, X D : Zhang, J M : Yang, H H : Hu, G Y. Modulation of NMDA receptor by huperzine A in rat cerebral cortex. Zhongguo Yao Li Xue Bao. 1999 Jan;20(1):31-5
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Ye, J W : Cai, J X : Wang, L M : Tang, X C. Improving effects of huperzine A on spatial working memory in aged monkeys and young adult monkeys with experimental cognitive impairment. -Pharmacol-Exp-Ther. 1999 Feb; 288(2): 814-9
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Cereprotectin® (proprietary blend of the following 7 natural supplements in BriteSHIELD®)
R-Alpha Lipoic Acid (R-ALA) is the R form of ALA, and is believed to be (perhaps significantly) more biologically active than the S form. Normal alpha lipoic acid ( ALA) is racemic meaning it contains 50% the R form and 50% the S form. R-ALA is a powerful antioxidant at the mitochondrial level where its ability to tame the fires and free radicals of the oxidative, energy generating process is highly essential to protect the mitochondria from burn out. ALA revitalizes, or recycles other neuro-protective, anti-oxidant agents, such as Vitamins C and E, and CoQ10. It increases brain levels of glutathione, an important antioxidant, brain protector and immune system booster. ALA also improves blood sugar balance, lowers insulin resistance, and reduces the glycation of proteins, or AGE plaque formation. It has been shown to improve memory and actually reverse neuropathy. ALA, when combined with acetyl-l-carnitine has shown remarkable synergistic effects in slowing down brain aging at the mitochondrial level.
Thirunavukkarasu V, Anitha Nandhini AT, Anuradha CV. Lipoic acid improves glucose utilisation and prevents protein glycation and AGE formation. Pharmazie. October 2005, Vol. 60, Issue: 10, Page(s): 772-775 (See Details)
Thirunavukkarasu,-V; Anitha-Nandhini,-A-T; Anuradha,-C-V. Lipoic acid attenuates hypertension and improves insulin sensitivity, kallikrein activity and nitrite levels in high fructose-fed rats. J-Comp-Physiol-[B]. 2004 Nov; 174(8): 587-92 (See Details)
Midaoui,-A-E; Elimadi,-A; Wu,-L; Haddad,-P-S; de-Champlain,-J. Lipoic acid prevents hypertension, hyperglycemia, and the increase in heart mitochondrial superoxide production. Am-J-Hypertens. 2003 Mar; 16(3): 173-9 (See Details)
Farr, S A : Poon, H F : Dogrukol Ak, D : Drake, J : Banks, W A : Eyerman, E : Butterfield, D A : Morley, J E. The antioxidants alpha-lipoic acid and N-acetylcysteine reverse memory impairment and brain oxidative stress in aged SAMP8 mice. J-Neurochem. 2003 Mar; 84(5): 1173-83 (See Details)
Liu, Jiankang : Killilea, David W : Ames, Bruce N. Age-associated mitochondrial oxidative decay: improvement of carnitine acetyltransferase substrate-binding affinity and activity in brain by feeding old rats acetyl-L- carnitine and/or R-alpha -lipoic acid. Proc-Natl-Acad-Sci-U-S-A. 2002 Feb 19; 99(4): 1876-8 (See Details)
Liu, Jiankang : Head, Elizabeth : Gharib, Afshin M : Yuan, Wenjun : Ingersoll, Russell T : Hagen, Tory M : Cotman, Carl W : Ames, Bruce N. 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-alpha -lipoic acid. Proc-Natl-Acad-Sci-U-S-A. 2002 Feb 19; 99(4): 2356-61 (See Details)
Arivazhagan, P : Shila, S : Kumaran, S : Panneerselvam, C. Effect of DL-alpha-lipoic acid on the status of lipid peroxidation and antioxidant enzymes in various brain regions of aged rats. Exp-Gerontol. 2002 Jun; 37(6): 803-11 (See Details)
Pirlich, M : Kiok, K : Sandig, G : Lochs, H : Grune, T. Alpha-lipoic acid prevents ethanol-induced protein oxidation in mouse hippocampal HT22 cells. Neurosci-Lett. 2002 Aug 9; 328(2): 93-6 (See Details)
Flier, J : Van Muiswinkel, F L : Jongenelen, C A : Drukarch, B. The neuroprotective antioxidant alpha-lipoic acid induces detoxication enzymes in cultured astroglial cells. Free-Radic-Res. 2002 Jun; 36(6): 695-9 (See Details)
Arivazhagan, P : Ramanathan, K : Panneerselvam, C. Effect of DL-alpha-lipoic acid on glutathione metabolic enzymes in aged rats. Exp-Gerontol. 2001 Dec; 37(1):81-7 (See Details)
Zhang, L : Xing, G Q : Barker, J L : Chang, Y : Maric, D : Ma, W : Li, B S : Rubinow, D R. Alpha-lipoic acid protects rat cortical neurons against cell death induced by amyloid and hydrogen peroxide through the Akt signalling pathway. Neurosci-Lett. 2001 Oct 26; 312(3): 125-8 (See Details)
Arivazhagan, P : Ramanathan, K : Panneerselvam, C. Effect of DL-alpha-lipoic acid on mitochondrial enzymes in aged rats. Chem-Biol-Interact. 2001 Nov 28; 138(2): 189-98 (See Details)
N-Acetyl-Cysteine (NAC): an amino acid with powerful neuroprotective and anti-oxidant actions, even down at the mitochondrial level. NAC is a precursor of glutathione, one of the most powerful endogenous immune enhancers. NAC and glutathione fight brain inflammation as well as free radicals. NAC also chelates heavy metals, such as lead and mercury, lightening their toxic load on the brain. NAC lowers brain damaging homocysteine levels. Some studies suggest that combining NAC with other anti-oxidants and the B vitamins significantly reduces the risk for developing Alzheimer’s later in life. In fact, NAC has been shown to improve cognitive function in a group with elevated homocysteine, an acknowledged brain toxin.
Adair JC, Knoefel JE, Morgan N. Controlled trial of N-acetyl-cysteine for patients with probable Alzheimer's disease. Neurology. 2001 Oct 23;57(8):1515-7.
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Susan A. Farr, H. Fai Poon, Dilek Dogrukol-Ak, Jeniffer Drake, William A. Banks, Edward Eyerman,D. Allan Butterfield‡ and John E. Morley.The antioxidants a-lipoic acid and N-acetylcysteine reverse memory impairment and brain oxidative stress in aged SAMP8 mice. Journal of Neurochemistry 2003; 84(5);1173.
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M. Zafarullah A, W. Q. Li A, J. Sylvester A, M. Ahmad A. Molecular mechanisms of N-acetylcysteine actions. Cellular and Molecular Life Sciences (CMLS) 2003;60(1); 6-20.
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Mushfiquddin Khan, Bipanjeet Sekhon, Manu Jatana, Shailendra Giri, Anne G. Gilg, Charanpal Sekhon, Inderjit Singh, Avtar K. Singh. Administration of N-acetylcysteine after focal cerebral ischemia protects brain and reduces inflammation in a rat model of experimental stroke.
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Sekhon B, Sekhon C, Khan M, Patel SJ, Singh I, Singh AK.N-Acetyl-cysteine protects against injury in a rat model of focal cerebral ischemia. Brain Res. 2003 May 2;971(1):1-8.
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Lizard G, Miguet C, Bessede G, Monier S, Gueldry S, Neel D, Gambert P. Impairment with various antioxidants of the loss of mitochondrial transmembrane potential and of the cytosolic release of cytochrome c occuring during 7-ketocholesterol-induced apoptosis. Free Radic Biol Med. 2000 Mar 1;28(5):743-53.
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Banaclocha MM.Therapeutic potential of N-acetyl-cysteine in age-related mitochondrial neurodegenerative diseases. Med Hypotheses. 2001 Apr;56(4):472-7.
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Quercetin is a dietary flavonoid found in many plants, including tea, apple, onion, ginkgo biloba and citrus.
Quercetin forms the "backbone" for many other flavonoids, including the citrus flavonoids rutin, hesperidin, naringin and tangeritin. In studies, Quercetin is found to be the most active of the flavonoids, and many medicinal plants owe much of their activity to their high quercetin content. Quercetin has demonstrated significant anti-inflammatory activity because of direct inhibition of several stages and processes of inflammation. In addition, it exerts potent antioxidant activity and boosts the effectiveness of vitamin C.
Quercetin has antioxidant, anti-inflammatory, nitric oxide inhibitor, and tyrosine kinase inhibitor (leading to inhibition of the division and growth of T-cells and some cancer cells) activity. The anti-inflammatory effects of quercetin appear to be due to inhibition of the production and activity of leukotrienes and prostaglandins, and inhibition of histamine. Quercetin also appears to reduce capillary fragility.
Quercetin’s broad spectrum anti-oxidant and anti-inflammatory actions make it one of the best cytoprotective and neuroprotective molecules found in nature.
Abd-El-Gawad HM & Califa AE. Quercetin, coenzyme Q10 and L-canavanine as protective agents against lipid peroxidation and nitric oxide generation in endotoxin-induced shock in rat brain. Pharmacological Research 2001, 43: 257-263.
Bastianetto S & Quirion R. Natural extracts as possible protective agents of brain aging. Neurobiology of Aging 2002, 23: 891- 897.
Esposito E, Rotilio D, Di Matteo V, Di Giulio C, Cacchio M & Algeri S. A review of specific dietary antioxidants and the effects on biochemical mechanisms related to neurodegenerative processes. Neurobiology of Aging, 2002, 23: 719-735
Jae Sue Choi, Hae Young Chung, Sam Sik Kang, Mee Jung Jung, Jung Won Kim, Jae Kyung No, Hyun Ah Jung. The structure-activity relationship of flavonoids as scavengers of peroxynitrite. Phytotherapy Research 2002:16(3);232 - 235.
Juurlink BH & Paterson PG. Review of oxidative stress in brain and spinal cord injury: suggestions for pharmacological and nutritional management strategies. Journal of Spinal Cord Medicine, 200221: 309-334.
Lean ME, Noroozi M, Kelly I. Dietary flavonols protect diabetic human lymphocytes against oxidative damage to DNA. Diabetes 1999;48:176-81.
Oyama Y, Fuchs PA, Katayama N, Noda K. Myricetin and quercetin, the flavonoid constituents of Ginkgo biloba extract, greatly reduce oxidative metabolism in both resting and Ca(2+)-loaded brain neurons. Brain Res. 1994 Jan 28;635(1-2:125-9.
Resveratrol (RES) is a flavonoid found in more than 70 plants including Asian herbs, grapevine, grapes, peanuts and berries. Recent data suggest that nutritional intake of resveratrol may contribute to the "French paradox", the unexpectedly low cardiovascular morbidity in the Mediterranean population. There is increasing evidence that resveratrol exerts multifaceted anti-oxidant and anti-inflammatory effects in the brain. Importantly, resveratrol was reported to slow aging and increase lifespan in simple organisms and has been suggested as a potential calorie restriction mimetic and anti-aging nutrient.
RES has been found to protect the brain against the neurotoxic and degenerative effects of beta amyloid (aka Abeta), the neurotoxic protein that builds up in the brain tissue of people with Alzheimer's disease and kill neurons.
One of Resveratrol’s most potent effects is its ability to block Nuclear Factor kappaBeta. NF-kB as an important contributor to the destructive power of amyloid beta plaques in the brain. RES also reduces destructive inflammation in the microglial, part of the white matter which act’s as the brain’s immune system.
Resveratrol’s demonstrated anti-aging effects derive from its apparent ability to activate important sirtuins, especially Sir2 enzymes which have been shown to promote cell survival and longevity in lower organisms.
Egemen Savaskan, Gianfranco Olivieri, Fides Meier, Erich Seifritz, Anna Wirz-Justice, Franz Müller-Spahn. Red Wine Ingredient Resveratrol Protects from - Amyloid Neurotoxicity. Gerontology 2003;49:380-383.
HEAN ZHUANG, YUN-SOOK KIM, RAYMOND C. KOEHLER and SYLVAIN DORÉ. Potential Mechanism by Which Resveratrol, a Red Wine Constituent, Protects Neurons. Ann. N.Y. Acad. Sci. 993: 276-286 (2003).
Inoue H, Jiang XF, Katayama T, Osada S, Umesono K, Namura S. Brain protection by resveratrol and fenofibrate against stroke requires peroxisome proliferator-activated receptor alpha in mice. Zhonghua Yi Xue Za Zhi. 2003 Apr 10;83(7):534-6.
Labinskyy N, Csiszar A, Veress G, Stef G, Pacher P, Oroszi G, Wu J, Ungvari Z. Vascular dysfunction in aging: potential effects of resveratrol, an anti-inflammatory phytoestrogen. J. Biol. Chem., Vol. 280, Issue 17, 17187-17195, April 29, 2005.
Labinskyy N, Csiszar A, Veress G, Stef G, Pacher P, Oroszi G, Wu J, Ungvari Z. Vascular dysfunction in aging: potential effects of resveratrol, an anti-inflammatory phytoestrogen. Curr Med Chem. 2006;13(9):989-96.
Margie T. Borra, Brian C. Smith, and John M. Denu. Mechanism of Human SIRT1 Activation by Resveratrol* Neurosci Lett. 2000 Mar 10;281(2-3):123-6.
Virgili M, Contestabile A. Partial neuroprotection of in vivo excitotoxic brain damage by chronic administration of the red wine antioxidant agent, trans-resveratrol in rats. Neurosci Lett. 2003 Dec 11;352(3):203-6.
Wang YJ, He F, Li XL. The neuroprotection of resveratrol in the experimental cerebral ischemia. Annals of the New York Academy of Sciences 993:276-286 (2003).
MethylCobalamin (Vitamin B12) is a co-enzyme, methyl form of Vitamin B-12 that is more specific to the central nervous system and brain than the standard, supplemental synthetic form of B-12, cyancobalamin.
Vitamin B12 is used orally for anemia, aging, improving concentration, mood elevation, boosting energy, and raising energy levels.
The methylcobalamin form of vitamin B12 is required in one of the pathways for homocysteine (Hcy) metabolism. Elevated Hcy levels have been implicated in accelerated cognitive decline, memory loss, and Alzheimer’s. METHC plus vitamin B-6 and folic acid can lower Hcy and improve brain health and cognitive performance.
METHC has other unique properties. For one it’s a neuroprotective agent which means it can help neutralize the brain damaging effects of certain neurotoxins such as, calciumoverload in the brain cells. It also helps accelerate the repair of damaged neural tissue which takes place daily as a result of aging, lifestyle excesses, free radicals and oxidative stress, inflammation and calcium overload.
Methylcobalamin may even regenerate brain cell connections called axons. These, as well as dendrites are the “wires, or cables” that enable neurons to communicate with each other. METHC also supports synthesis of the myelin sheath which is the vital electrical insulation of the brain’s axons. This helps the brain communicate your perceptions, thoughts, memories, decisions and emotions faster and more efficiently throughout more of the brain.
Vitamin B12 is involved in fat and carbohydrate metabolism and protein synthesis. Vitamin B12 is essential for folate utilization, and its absence results in a functional folate deficiency. Vitamin B-12 deficiency may be a predominant cause of, or at least major contributor to cognitive dysfunction and memory loss, especially with vegetarians and seniors. For one, as we age the intestinal absorption of B-12 from foods is reduced. Secondly, older people and of course, vegetarians tend to eat less animal protein which is a primary source of B-12.
Some researchers think that vitamin B12 supplements could help symptoms of chronic fatigue syndrome by correcting red blood cell abnormalities and improving oxygen delivery to tissues. The methylcobalamin form of vitamin B12 might also influence melatonin levels. Methylcobalamin seems to improve alertness and reduce sleep time in humans with normal sleep patterns, possibly due to effects on melatonin.
Brenda W. J. H. Penninx et al. "Vitamin B12 Deficiency and Depression in Physically Disabled Older Women: Epidemiologic Evidence From the Women’s Health and Aging Study". Am. J. Psychiatry, 2000; 157: 715–721. PMID 10784463.
Clarke R. Prevention of vitamin B-12 deficiency in old age. Am J Clin Nutr. 2001;73:151-152.
Duthie SJ, Whalley LJ, Collins AR, et al. Homocysteine, B vitamin status, and cognitive function in the elderly. Am J Clin Nutr 2002;75:908-13.
Huff A. Vitamin B12 and cognitive impairment.
Lerner V, Kanevsky M. Acute dementia with delirium due to vitamin B12 deficiency: a case report.Int J Psychiatry Med. 2002;32(2):215-20
Louwman MW, van Dusseldorp M, van de Vijver FJ, et al. Signs of impaired cognitive function in adolescents with marginal cobalamin status. Am J Clin Nutr 2000;72:762-9.
Masuda Y, Kokubu T, Yamashita M, Ikeda H, Inoue S. EGG phosphatidylcholine combined with vitamin B12 improved memory impairment following lesioning of nucleus basalis in rats. Life Sci. 1998;62(9):813-22
Mayer G, Kroger M, Meier-Ewert K. Effects of vitamin B12 on performance and circadian rhythm in normal subjects. Neuropsychopharmacology 1996;15:456-64.
Sunder-Plassmann G, Winkelmayer WC, Fodinger M. Therapeutic potential of total homocysteine-lowering drugs on cardiovascular disease. Exp Opin Invest Drugs 2000;9:2637-51.
van Asselt DZ, Pasman JW, van Lier HJ, Vingerhoets DM, Poels PJ, Kuin Y, Blom HJ, Hoefnagels WH. Cobalamin supplementation improves cognitive and cerebral function in older, cobalamin-deficient persons.J Gerontol A Biol Sci Med Sci. 2001 Dec;56
Werbach MR. Nutritional strategies for treating chronic fatigue syndrome. Altern Med Rev 2000;5:93-108.
Curcumin (CUR) : The active polyphenol compound in the bright yellowish orange spice, Turmeric, CUR is a powerful COX-2 inhibitor. It also reduces brain inflammation via other pathways such as, LOX-5 as well as highly damaging NOS (nitric oxide) based peroxynitrites. CUR is also a powerful anti-oxidant and neuro-protective agent. Perhaps most remarkably it has demonstrated the ability to reduce and prevent the formation of the telltale Alzheimer’s plaques known as beta amyloid, or Abeta. In fact, studies even revealed that CUR can reduce the existing plaque burden of Abeta.
Subramanian M, Sreejayan, Rao MN, Devasagayam TP, Singh BB. Diminution of singlet oxygen-induced DNA damage by curcumin and related antioxidants. Mutat Res 1994; 11:249–255.
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Huang MT, Lysz T, Ferraro T, Abidi TF, Laskin JD, Conney AH. Inhibitory effects of curcumin on in vitro lipoxygenase and cyclooxygenase activities in mouse epidermis. Cancer Res 1991; 51: 813–819.
Zhao BL, Li XJ, He RG, Cheng SJ, Xin WJ. Scavenging effect of extracts of green tea and natural antioxidants on active oxygen radicals. Cell Biophys 1989; 14:175–185.
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Yamamoto H, Hanada K, Kawasaki K, Nishijima M. Inhibitory effect of curcumin on mammalian phospholipase D activity. FEBS. Letters 1997; 417:196–198.
Rao CV, Rivenson A, Simi B, Reddy BS. Chemoprevention of colon carcinogenesis by dietary curcumin, a naturally occurring plant phenolic compound. Cancer Res 1995; 55:259–266.
Xu YX, Pindolia KR, Janakiraman N, Chapman RA, Gautam SC. Curcumin inhibits IL1 alpha and TNF-alpha induction of AP-1 and NF-kB DNA-binding activity in bone marrow stromal cells. Hematopathol Mol Hematol 1998; 11:49–62.
Huang TS, Lee SC, Lin JK. Suppression of c-Jun/AP-1 activation by an inhibitor of tumor promotion in mouse fibroblast cells. Proc Natl Acad Sci USA 1991; 88:5292–5296.
Lim GP, Chu T, Yang F, Beech W, Frautschy SA, Cole GM. The curry spice curcumin reduces oxidative damage and amyloid pathology in an Alzheimer transgenic mouse. J Neurosci 2001; 21: 8370–8377.
Ruby AJ, Kuttan G, Babu KD, Rajasekharan KN, Kuttan R. Antitumour and antioxidant activity of natural curcuminoids. Cancer Letters 1995; 94:79–83.
Scapagnini G, Foresti R, Calabrese V, Giuffrida Stella AM, Green CJ, Motterlini R. Caffeic acid phenethyl ester and curcumin: A novel class of heme oxygenase-1 inducers. Mol Pharmacol 2002; 61:554–561.
Soliman KFA, Mazzio EA. In vitro attenuation of nitric oxide production in C6 astrocyte cell culture by various dietary compounds. Proc Soc Exp Biol Med 1998; 218:390–397.
Frautschy SA, Hu W, Kim P, Miller SA, Chu T, Harris-White ME, Cole GM. Phenolic anti-inflammatory antioxidant reversal of Abeta-induced cognitive deficits and neuropathology. Neurobiol Aging 2001; 22:993–1005.
Rowe B, Ronzio RA, Wellner VP, Meister A. Glutamine Synthetase (Sheep Brain). Meth Enzymol 1970; 17:900–902.
Prohaska JR, Clark DA, Wells WW. Improved rapidity and precision in the determination of brain 2’,3’-cyclic nucleotide 3’- phosphohydrolase. Anal Biochem 1973; 56:275–82.
Griffin WST, Sheng JG, Royston MC, Gentleman SM, McKenzie JE, Graham DI, et al. Glial-neuronal interactions in Alzheimer’s disease: the potential role of a ‘cytokine cycle’ in disease progression. Brain Pathol 1998; 8:65–72.
Bioperine is the brand name for a Black Pepper fruit extract (98% piperine) that has been shown to enhance the bioavailability of certain nutrients including the Curcumin and possibly Quercetin found in BriteSHIELD®.