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Blueberry Extract
Blueberry Extract
Blueberry Extract

Blueberry Extract

Brain & Nerve Health

$141.98

The Brain is the center of our personal universe, controlling and effecting all the systems in the body, including motor functions (balance, strength or frailty), immunity, and of course, how we think. Foggy brain, memory lapses, and cognitive decline are effecting the old and young populations alike.

Scientists describe blueberries’ polyphenols as essential agents of neuro-regeneration and repair. Research studies show that a daily intake of at least 1 cup of blueberries offer important regenerative support for a healthy brain.*

The Blueberry Extract is potent: It takes 80 pounds of blueberries to get one pound of the pure purple extract. One capsule of the polyphenolic extract is equivalent to a cup and a quarter of whole blueberries!*

Our Blueberry Extract stands alone. 100% North American blueberry extract (Vaccinium corymbosum) provides a daily comprehensive profile of polyphenols to feed your brain.*

The Blueberry Extract is Pure, Vegan, Kosher, and Non GMO.

The Blueberry Extract offers the highest concentration of the North American blueberry species, Vaccinium corymbosum, with a significant broad-spectrum phenolic profile.

The Blueberry Extract is a powerful concentration of anthocyanins: It takes eighty pounds of blueberries to get one pound of the pure purple extract. This means that one capsule of the extract is equivalent to a cup and a quarter of whole blueberries.

Each vegan capsule has 500mg of the pure extract, without any excipients or fillers.

Tuft University’s James Joseph and Barbara Shukitt-Hale have researched the use and application of blueberries as a potential therapeutic agent for many years. Their studies along with their colleagues demonstrate that blueberries and blueberry extract reverse and prevent brain aging (Shukitt-Hale et al., 2008; 2007), improve memory and motor skills (Carey et al., 2014; Malin et al., 2011; Brewer et al., 2010), repair neuronal tissue and function (Joseph et al., 2003; Miller et al., 2012), and serve as a potent anti-aging food (Joseph et al., 1999; 2009; Shukitt-Hale et al., 2015; 2012).*

The Blueberry Extract was designed with Dr. Joseph’s assistance by converting some of the data from his research to human consumption.*

Steward, Sridhar, and Meyer (2013) define regeneration of the nerves as a process of repairing or replacing nerve cells that have been damaged. Studies have hypothesized that an antioxidant-enriched diet may affect neuro-regeneration and inhibit inflammation due to their high anthocyanins (Szajdek & Borowska, 2008; Sweeney et al., 2002).*

Research studies and reviews by Latif (2015), Panickar & Anderson (2010), Subash et al. (2014), Panickar (2013), Schaffer et al. (2006), and Letenneur et al. (2007), demonstrate the great ability of flavonoids to offer a consistent neuro-protective nutriceutical.

Stratheam et al. (2014) demonstrate that anthocyanin rich extracts of blueberries and grape seed support the process of neuro re-generation by interfering with the neurotoxin, rotenone, and improving the mitochondrial function. Gao et al. (2012) find that a habitual intake of dietary flavonoids is associated with a lower risk of developing neurological issues, such as Parkinson, or lessening brain edema (Panickar & Anderson, 2010). Kovacsova et al. (2010) researched the biochemical pathways and molecular neuro-protective mechanisms of polyphenols in the brain. Antioxidant activity reduces neuro-inflammation and supports the prevention of neuro-degeneration (Stromberg et al., 2005). Williams & Spencer (2012) and Galli et al. (2006) show that a blueberry-supplemented diet reverses age-related declines with improved cognition and nerve regeneration.*

The process of neurological regenerative ability of blueberries is linked to their potent anti-inflammatory and antioxidant properties (Subash et al., 2014; Duffy et al., 2008; Shukitt-Hale et al., 2008), effecting the reduction of NF Kappa beta, Cox-2 and Isoprostane (Youdim et al., 2002). For this reason, studies emphasize the important dietary role of blueberries, as anthocyanins are able to reduce oxidative stress and anti-inflammatory cytokines (McAnulty et al., 2011).*

Due to their high levels of anthocyanins, blueberries are also shown in research to contribute to heart health (McAnulty, 2014; Louis et al., 2014; Erlund et al., 2008; Youdim & Joseph, 2001).*

How available are these anthocyanins? Mazza et al. (2002) has demonstrated that consumption of blueberries raises blood serum ORAC (antioxidant capacity). Emerging evidence confirms the ability of the human body to absorb anthocyanins, demonstrating a greater bioavailability (Bell et al., 2015), prolonged circulation, and relatively high concentration of anthocyanins metabolites (Lila et al., 2016).*

See the Research tab for additional bibliography to further understand the application and use of blueberry and blueberry extract.

*These statements have not been evaluated by the Food & Drug Administration. This products is not intended to diagnose, treat, cure or prevent any disease. The information and citations of research are for informational purposes only. Please be sure to consult your health care provider before taking this or any other product.

REFERENCES

Erlund, I., Koli, R., Alfthan, G., Marniemi, J., Puukka, P., Mustonen, P… Jula, A. (2008). Favorable effects of berry consumption on platelet function, blood pressure, and HDL cholesterol. Am J Clin Nutr 87, 323-331. Article

Galli, R.L., Bielinski, D.F., Szprengiel, A., Shukitt-Hale, B., Joseph, J.A. (2006). Blueberry supplemented diet reverses age-related decline in hippocampal HSP70 neuroprotection. Neurobio Aging, 27, 344-350. DOI:10.1016/j.neurobiolaging.2005.01.017

Gao, X., Cassidy, A., Schwarzschild, M.A., Rimm, E.B., & Ascherio, A. (2012). Habitual intake of dietary flavonoids and risk of Parkinson disease. Neurology, 78(10), 1138-45. doi: 10.1212/WNL.0b013e31824f7fc4

Joseph, J., Cole, G., Head, E., Ingram, D. (2009). Nutrition, brain aging, and neurodegeneration. J. Neurosci. 29(41), 12795–12801. DOI: 10.1523/JNEUROSCI.3520-09.2009

Joseph, J.A., Shukitt-Hale, B., & Lau, F.C. (2007). Fruit polyphenols and their effects on neuronal signaling and behavior in senescence . Ann NY Acd Sci, 1100, 470-85. DOI: 10.1196/annals.1395.052

Joseph, J.A., Denisova, N.A., Arendash, G., Gordon, M., Diamond, D., Shukitt-Hale, B., Morgan, D. (2003). Blueberry supplementation enhances signaling and prevents behavioral deficits in an Alzheimer disease model. Nutr Neurosci, 6 (3), 153-162. DOI:10.1080/1028415031000111282

Joseph, J.A., Shukitt-Hale, B., Denisova, N.A., Bielinski, D., Martin, A., McEwen, J.J., & Bickford, P.C. (1999). Reversals of age-related declines in neuronal signal

Joseph, J., Cole, G., Head, E., Ingram, D. (2009). Nutrition, brain aging, and neurodegeneration. J. Neurosci. 29(41), 12795–12801. DOI: 10.1523/JNEUROSCI.3520-09.2009

Kovacsova, M., Barta, A., Parohova, J., Vrankova, S., Pechanova, O. (2010). Neuroprotective mechanisms of natural polyphenolic compounds. Act Nerv Super Rediviva, 52, 181-186. Abstract

Latif, R. (2015). Flavonoids as novel neuroprotective nutraceuticals. Saudi J Health Sci, 4, 1-4. DOI:10.4103/2278-0521.151402

McAnulty, L.S. Nieman, D.C., Dumke, C.L., Shooter, L.A., Henson, D.A., Utter, A.C., … McAnulty, S.R. (2011). Effect of blueberry ingestion on natural killer cell counts, oxidative stress, and inflammation prior to and after 2.5 h of running. Appl Physio Nutr Metab, 36(6), 976-84. DOI:10.1139/h11-120

Panickar, K.S., & Jang, S. (2013). Dietary and plant polyphenols exert neuroprotective effects and improve cognitive function in cerebral ischemia. Recent Pat Food Nutr Agric, 5(2), 128-43. DOI: 10.2174/1876142911305020003

Schaffer, S., Eckert, G.P., Schmitt-Schilling, S., & Muller, W.E. (2006). Plant foods and brain aging: a critical appraisal.Forum Nutr, 59, 86-115. DOI: 10.1159/000095209

Shukitt-Hale, B., Bielinski, D.F., Lau, F.C., Willis, L.M., Carey, A.N., & Joseph, J.A. (2015). The beneficial effects of berries on cognition, motor behaviour and neuronal function in ageing. Br J Nutr, 114 (10), 1542-9.DOI: 10.1017/S0007114515003451

Shukitt-Hale, B. (2012). Blueberries and neuronal aging.Gerontology, 58, 518-523. DOI: 10.1159/000341101

Shukitt-Hale, B., Lau, F.C., Joseph, J.A. (2008). Berry fruit supplementation and the aging brain. Journal of Agricultural and Food Chemistry, 56, 636–641. DOI10.1021/jf072505f

Shukitt-Hale, B., Carey, A.N., Jenkins, D., Rabin, B.M., Joseph, J.A. (2007). Beneficial effects of fruit extracts on neuronal function and behavior in a rodent model of accelerated aging. Neurobiol Aging, 28, 1187-1194. DOI: 10.1016/j.neurobiolaging.2006.05.031

Steward, M.N., Sridhar, A., & Meyer, J.S. (2013). Neural regeneration. Curr Top Microbiol Immunol, 367, 163-91. DOI: 10.1007/82_2012_302.

Strathearm, K.D., Yousef, G.G., Grace, M.H., Tambe, M.A., Ferruzzi, M.G., Wu, Q.L., Simon, J.E., Lila, M.A., & Rochet, J.C. (2014). Neuroprotective effects of anthocyanin-and proanthocyanidin-rich extracts in cellular models of Parkinson’s diseases. Brain Res, 1555, 60-77. . DOI: 10.1016/j.brainres.2014.01.047

Subash, S., Essa, M.M., Al-Adwi, S., Memon, M.A., Manivasagan, T., & Akbar, M. (2014). Neuroprotective effects of berry fruits on neurodegenerative diseases. Neural Regeneration Research, 9(16), 1557-1566. . DOI:10.4103/1673-5374.139483

Sweeney, M.I., Kalt, W., MacKinnon, S.L., Ashby, J., Gottschall-Pass, K.T. (2002) Feeding rats diets enriched in lowbush blueberries for six weeks decreases ischemia-induced brain damage. Nutr Neurosci 5, 427- 431. DOI: 10.1080/1028415021000055970

Youdim, K.A., Joseph, J.A. (2001). A possible emerging role of phytochemicals in improving age-related neurological dysfunctions: a multiplicity of effects. Free Radic Biol Med, 30, 583-594. http://doi.org/10.1016/S0891-5849(00)00510-4

FOOD SCIENCE: THE APPLICATION AND USE OF BLUEBERRY AND BLUEBERRY EXTRACT.*

Blueberry and Cognitive Support

Brewer, G.J., Torricelli, J.R., Lindsey, A.L., Kunz, E.Z., Neuman, A., Fisher, D.R., & Joseph, J.A. (2010). Age-related toxicity of amyloid-beta associated with increased pERK and pCREB in primary hippocampal neurons: reversal by blueberry extract. J Nutr Biochem, 21, 991-998. DOI: 10.1016/j.jnutbio.2009.08.005

Carey, A.N., Gomes, S.M., & Shukitt-Hale, B. (2014). Blueberry supplementation improves memory in middle-aged mice fed a high-fat diet. J Agric Food Chem, 62, 3972-3978. DOI: 10.1021/jf404565s

Casadesus, G., Shukitt-Hale, B., Stellwagen, H.M., Zhu, X., Lee, H.G., Smith, M.A., Joseph, J.A. (2004). Modulation of hippocampal plasticity and cognitive behavior by short-term blueberry supplementation in aged rats. Nutr Neurosci, 7, 309-316. DOI:10.1080/10284150400020482

Chemiack, E.P. (2012). A berry thought-provoking idea: the potential role of plant polyphenols in the treatment of age-related cognitive disorder. Br J Nutr, 108(5), 794-800. DOI: 10.1017/S0007114512000669

Devore, E.E., Kang, J.H., Breteler, M.M., & Grodstein, F. (2012). Dietary intakes of berries and flavonoids in relation to cognitive decline. Ann Neurol, 72(1), 135-43. DOI:10.1002/ana.23594

Duffy, K.B., Spangler, E.L., Devan, B.D., Guo, Z., Bowker, J.L., Janas, A.M., Hagepanos, A., Minor, R.K., DeCabo, R., Mouton, P.R., Shukitt-Hale, B., Joseph, J.A., Ingram, D.K. (2008). A blueberry-enriched diet provides cellular protection against oxidative stress and reduces a kainate-induced learning impairment in rats. Neurobiol Aging, 29, 1680-1689. DOI: 10.1016/j.neurobiolaging.2007.04.002

Goyarzu, P., Malin, D.H., Lau, F.C., Taglialatela, G., Moon, W.D., Jennings, R., Moy, E., Moy, D., Lippold, S., Shukitt-Hale, B., Joseph, J.A. (2004). Blueberry supplemented diet: effects on object recognition memory and nuclear factor-kappa B levels in aged rats. Nutr Neurosci, 7, 75-83. DOI: 10.1080/10284150410001710410

Joseph, J.A., Shukitt-Hale, B., & Lau, F.C. (2007). Fruit polyphenols and their effects on neuronal signaling and behavior in senescence . Ann NY Acd Sci, 1100, 470-85. DOI: 10.1196/annals.1395.052

Joseph, J.A., Shukitt-Hale, B., Denisova, N.A., Bielinski, D., Martin, A., McEwen, J.J., & Bickford, P.C. (1999). Reversals of age-related declines in neuronal signal transduction, cognitive, and motor behavioral deficits with blueberry, spinach, or strawberry dietary supplementation. J Neurosci, 19(18), 8114-21. . Article

Krikorian, R., Shidler, M.D., Nash, T.A., Kalt, W., Vingvist-tymchuk, M.R., Shukitt-Hale, B., Joseph, J.A. (2010). Blueberry supplementation improves memory in older adults. J. Agric Food Chem, 58, 3996-4000. DOI: 10.1021/jf9029332

Letennuur, L., Proust-Lima, C., Le Gouge, A., Dartigues, J.F., & Barberger-Gateau, P. (2007). Flavonoid intake and cognitive decline over a 10-year period. Am J Epideminol, 165(12), 1364-71. DOI: 10.1093/aje/kwm036

Malin, D.H., Lee, D.R., Goyarzum P., Chang, Y.H., Ennis, L.J., Beckett, E., Shukitt-Hale, B., Joseph, J.A. (2011). Short-term blueberry-enriched diet prevents and reverses object recognition memory loss in aging rats. Nutrition, 27, 338-342. DOI: 10.1016/j.nut.2010.05.001

Poulose, S.M., carey, A.N., Shukitt-Hale, B. (2012). Improving brain signaling in aging: Could berries be the answer?Expert Rev Neurother, 12(8), 887-9. DOI: 10.1586/ern.12.86

Rendeiro, C., Vauzour, D., Rattray, M., Waffo-Téguo, P., Mérillon, J.M., Butler, L.T., Williams, C.M., & Spencer, J.P. (2013). Dietary levels of pure flavonoids improve spatial memory performance and increase hippocampal brain-derived neurotrophic factor. PLoS One, 8(5), e63535. DOI: 10.1371/journal.pone.0063535

Rendeiro, C., Vauzour, D., Kean, R.J., Butler, L.T., Rattray, M., Spencer, J.P., & Williams, C.M. (2012). Blueberry supplementation induces spatial memory improvements and region-specific regulation of hippocampal BDNF mRNA expression in young rats. Psychopharmacology (Berl), 223 (3), 319-30. DOI: 10.1007/s00213-012-2719-8 .

Rendeiro, C., Guerreiro, J.D., Williams, C.M., Spencer, J.P. (2012). Flavonoids as modulators of memory and learning: molecular interactions resulting in behavioural effects. Proc Nutr Soc, 71(2), 246-62. DOI: 10.1017/S0029665112000146

Schaffer, S., Eckert, G.P., Schmitt-Schilling, S., & Muller, W.E. (2006). Plant foods and brain aging: a critical appraisal. Forum Nutr, 59, 86-115. DOI: 10.1159/000095209

Shukitt-Hale, B., Bielinski, D.F., Lau, F.C., Willis, L.M., Carey, A.N., & Joseph, J.A. (2015). The beneficial effects of berries on cognition, motor behaviour and neuronal function in ageing. Br J Nutr, 114 (10), 1542-9.DOI: 10.1017/S0007114515003451

Shukitt-Hale, B. (2012). Blueberries and neuronal aging. Gerontology, 58, 518-523. DOI: 10.1159/000341101

Shukitt-Hale, B., Lau, F.C., Joseph, J.A. (2008). Berry fruit supplementation and the aging brain. Journal of Agricultural and Food Chemistry, 56, 636–641. DOI:10.1021/jf072505f

Spencer, J.P. (2010). The impact of fruit flavonoids on memory and cognition. Br J Nutr, 104(3), S40-7. DOI: 10.1017/S0007114510003934

Vauzour, D. (2014). Effect of flavonoids on learning, memory and neurocognitive performance: relevance and potential implications for Alzheimer's disease pathophysiology. J Sci Food Agric, 94(6), 1042-56. DOI: 10.1002/jsfa.6473

Willis, L.M., Shukitt-Hale, B., Joseph, J.A. (2009). Recent advances in berry supplementation and age-related cognitive decline. Curr Opin Clin Nutr Metab Care, 12(1), 91-4. DOI: 10.1097/MCO.0b013e32831b9c6e

BLUEBERRY AND NEURO-PROTECTIVE EFFECT

Baptista, F.I., Henriques, A.G., Silva, A.M., Wiltfang, J., & da Cruz e Silva, O.A. (2014). Flavonoids as therapeutic compounds targeting key proteins involved in Alzheimer's disease. ACS Chem Neurosci, 5(2), 83-92. DOI: 10.1021/cn400213r

Campos-Esparza, M.R., & Torres-Ramos, M.A. (2010). Neuroprotection by natural polyphenols: molecular mechanisms. Cent Nerv Syste Agents Med Chem, 10(4), 269-77. DOI: 10.2174/187152410793429728

Esposito, E., Rotilio, D., Di Matteo, V., Di Giulio, C., Cacchio, M., Algeri, S. (2012). A review of specific dietary antioxidants and the effects on biochemical mechanisms related to neurodegenerative processes. Neurobiol Aging, 23, 719-735.

http://doi.org/10.1016/S0197-4580(02)00078-7

Galli, R.L., Bielinski, D.F., Szprengiel, A., Shukitt-Hale, B., Joseph, J.A. (2006). Blueberry supplemented diet reverses age-related decline in hippocampal HSP70 neuroprotection. Neurobio Aging, 27, 344-350. DOI:

10.1016/j.neurobiolaging.2005.01.017

Gao, X., Cassidy, A., Schwarzschild, M.A., Rimm, E.B., & Ascherio, A. (2012). Habitual intake of dietary flavonoids and risk of Parkinson disease. Neurology, 78(10), 1138-45. doi: 10.1212/WNL.0b013e31824f7fc4

Giacalone, M., Di Sacco, F. Traupe, I., Topini, R., Forfori, F., & Giunta, F. (2011). Antioxidant and neuroprotective properties of blueberry polyphenols: A critical review. Nutr Neurosci, 14(3), 119-25. DOI: 10.1179/1476830511Y.0000000007

Fuentealba, J., Dibarrant, A.J., Fuentes-Fuentes, M.C., Saez-Orellana, F., Qunones, K., Guzman, L., … Aguayo, L.G. (2011). Syaptic failure and adenosine triphosphate imbalance induced by amyloid-β aggregates are prevented by blueberry-enriched polyphenols extracts. J Neurosci Res, 89(9), 1499-508. DOI: 10.1002/jnr.22679

Joseph, J., Cole, G., Head, E., Ingram, D. (2009). Nutrition, brain aging, and neurodegeneration. J. Neurosci. 29(41), 12795–12801. DOI: 10.1523/JNEUROSCI.3520-09.2009

Joseph, J.A., Denisova, N.A., Arendash, G., Gordon, M., Diamond, D., Shukitt-Hale, B., Morgan, D. (2003). Blueberry supplementation enhances signaling and prevents behavioral deficits in an Alzheimer disease model. Nutr Neurosci, 6 (3), 153-162. DOI:

10.1080/1028415031000111282

Joseph, J.A., Shukitt-Hale, B., Denisova, N.A., Bielinski, D., Martin, A., McEwen, J.J., Bickford, P.C. (1999). Reversals of age-related declines in neuronal signal transduction, cognitive, and motor behavioral deficits with blueberry, spinach, or strawberry dietary supplementation. J Neurosci 19, 8114-8121. Article

Kolosova, N.G., Shcheglova, T.V., Sergeeva, S.V., Loskutova, L.V. (2006) Long-term antioxidant supplementation attenuates oxidative stress markers and cognitive deficits in senescent-accelerated OXYS rats. Neurobiol Aging, 27, 1289-1297. DOI:10.1016/j.neurobiolaging.2005.07.022

Kovacsova, M., Barta, A., Parohova, J., Vrankova, S., Pechanova, O. (2010). Neuroprotective mechanisms of natural polyphenolic compounds. Act Nerv Super Rediviva, 52, 181-186. Abstract

Latif, R. (2015). Flavonoids as novel neuroprotective nutraceuticals. Saudi J Health Sci, 4, 1-4. DOI:10.4103/2278-0521.151402

Meng, X., Munishkina, L.A., Fink, A.L., Uversky, V.N. (2010). Effects of Various Flavonoids on the α-Synuclein Fibrillation Process. Parkinson Dis., 650794. DOI:10.4061/2010/650794

Miller, M.G., Shukitt-Hale, B. (2012). Berry fruit enhances beneficial signaling in the brain. J. Agric. Food Chem, 60(23), 5709–5715. DOI: 10.1021/jf2036033

Nile, S.H., Park, S.W. (2014). Edible berries: Bioactive components and their effect on human health. Nutrition, 30, 134-144. DOI: 10.1016/j.nut.2013.04.007

Ono, K., Yoshiike, Y., Takashima, A., Hasegawa, K., Naiki, H., & Ymada, M. (2003). Potent Anti-amyloidogenic and fibril-destabilizing effects of polyphenols in vitro: Implications for the prevention and therapeutics of Alzheimer’s isease. J Neurochem, 87, 172-181. . DOI:10.1046/j.1471-4159.2003.01976.x

Pandey, K.B., Rizv,i S.I. (2009). Plant polyphenols as dietary antioxidants in human health and disease. Oxid Med Cell Longev, 2, 270-278. doi: 10.4161/oxim.2.5.9498

Panickar, K.S., & Jang, S. (2013). Dietary and plant polyphenols exert neuroprotective effects and improve cognitive function in cerebral ischemia. Recent Pat Food Nutr Agric, 5(2), 128-43. DOI: 10.2174/1876142911305020003

Schaffer, S., Eckert, G.P., Schmitt-Schillig, S., Müller, W.E. (2006). Plant foods and brain aging: a critical appraisal. Forum Nutr, 59, 86-115. DOI: 10.1159/000095209

Schroeter, H., Boyd, C., Spencer, J.P., Williams, R.J., Cadenas, E., Rice-Evans, C. (2002). MAPK signaling in neurodegeneration: influences of flavonoids and of nitric oxide. Neurobiol Aging 23(5), 861–880. DOI: http://dx.doi.org/10.1016/S0197-4580(02)00075-1

Shukitt-Hale, B. (2012). Blueberries and neuronal aging. Gerontology, 58(6), 518-23. DOI: 10.1159/000341101.

Shukitt-Hale, B., Lau, F.C., Carey, A.N., Galli, R.L., Spangler, E.L., Ingram, D.K., Joseph, J.A. (2008). Blueberry polyphenols attenuate kainic acid-induced decrements in cognition and alter inflammatory gene expression in rat hippocampus. Nutr Neurosci, 11, 172-182. DOI: 10.1179/147683008X301487

Shukitt-Hale, B., Carey, A.N., Jenkins, D., Rabin, B.M., Joseph, J.A. (2007). Beneficial effects of fruit extracts on neuronal function and behavior in a rodent model of accelerated aging. Neurobiol Aging, 28, 1187-1194. DOI: 10.1016/j.neurobiolaging.2006.05.031

Spencer, J.P. (2010). Beyond antioxidants: the cellular and molecular interactions of flavonoids and how these underpin their actions on the brain. Proc Nutr Soc, 69(2):244-60. DOI: 10.1017/S0029665110000054

Spencer, J.P., Vauzour, D., Rendeiro, C. (2009). Flavonoids and cognition: the molecular mechanisms underlying their behavioural effects. Arch Biochem Biophys, 492(1-2):1-9 DOI: 10.1017/S0029665112000146

Steward, M.N., Sridhar, A., & Meyer, J.S. (2013). Neural regeneration. Curr Top Microbiol Immunol, 367, 163-91. DOI: 10.1007/82_2012_302

Strathearm, K.D., Yousef, G.G., Grace, M.H., Tambe, M.A., Ferruzzi, M.G., Wu, Q.L., Simon, J.E., Lila, M.A., & Rochet, J.C. (2014). Neuroprotective effects of anthocyanin-and proanthocyanidin-rich extracts in cellular models of Parkinson’s diseases. Brain Res, 1555, 60-77. . DOI: 10.1016/j.brainres.2014.01.047

Stromberg, I., Gemma, C., Vila, J., Bickford, P.C. (2005). Blueberry- and spirulina-enriched diets enhance striatal dopamine recovery and induce a rapid, transient microglia activation after injury of the rat nigrostriatal dopamine system. Exp Neurol, 196, 298-307. DOI: 10.1016/j.expneurol.2005.08.013

Subash, S., Essa, M.M., Al-Adwi, S., Memon, M.A., Manivasagan, T., & Akbar, M. (2014). Neuroprotective effects of berry fruits on neurodegenerative diseases. Neural Regeneration Research, 9(16), 1557-1566. . DOI:10.4103/1673-5374.139483

Sweeney, M.I., Kalt, W., MacKinnon, S.L., Ashby, J., Gottschall-Pass, K.T. (2002) Feeding rats diets enriched in lowbush blueberries for six weeks decreases ischemia-induced brain damage. Nutr Neurosci 5, 427- 431. DOI: 10.1080/1028415021000055970

Szajdek, A., Borowska, J.E. (2008). Bioactive compounds and health-promoting properties of berry fruits a review. Plant Foods Hum Nutr, 63,147-156. DOI:10.1007/s11130-008-0097-5

Wang, Y., Chang, C.F., Chou, J., Chen, H.L., Deng, X., Harvey, B.K., Cadet, J.L., Bickford, P.C. (2005). Dietary supplementation with blueberries, spinach, or spirulina reduces ischemic brain damage. Exp Neurol, 193, 75-84. DOI: 10.1016/j.expneurol.2004.12.014

Williams, C.M., El Mohsen, M.A., Vauzour, D., Rendeiro, C., Butler, L.T., Ellis, J.A., Whiteman, M., Spencer, J.P. (2008). Blueberry induced changes in spatial working memory correlate with changes in hippocampal CREB phosphorylation and brain-derived neurotrophic factor (BDNF) levels. Free Radical Biol Med, 45, 295-305. DOI:10.1016/j.freeradbiomed.2008.04.008

Williams, R.J. & Spencer, J.P. (2012). Flavonoids, cognition, and dementia: actions, mechanisms, and potential therapeutic utility for Alzheimer disease. Free Radic Biol Med, 52(1), 35-45. DOI: 10.1016/j.freeradbiomed.2011.09.010

Youdim, K.A., Joseph, J.A. (2001). A possible emerging role of phytochemicals in improving age-related neurological dysfunctions: a multiplicity of effects. Free Radic Biol Med, 30, 583-594. http://doi.org/10.1016/S0891-5849(00)00510-4

Youdim, K.A., Shukitt-Hale, B., Martin, A., Wang, H., Denisova, N., Bickford, P.C., Joseph, J.A. (2000). Short-term dietary supplementation of blueberry polyphenolics: beneficial effects on aging brain performance and peripheral tissue function. Nutr Neurosci, 3, 383-397. http://dx.doi.org/10.1080/1028415X.2000.11747338

SYSTEMIC ANTI-INFLAMMATORY SUPPORT

Akiyama et al. (2000). Inflammation and Alzheimer’s disease. Neurobiol Aging, 21(3), 383-421. doi: 10.1101/cshperspect.a006346

Grace, M.H., Esposito D., Dunlap K.L., & Lila M.A. (2014). Comparative analysis of phenolic content and profile, antioxidant capacity, and anti-inflammatory bioactivity in wild Alaskan and commercial Vaccinium berries. J Agric Food Chem, 62(18), 4007-17. doi: 10.1021/jf403810y.

McAnulty, L.S. Nieman, D.C., Dumke, C.L., Shooter, L.A., Henson, D.A., Utter, A.C., … McAnulty, S.R. (2011). Effect of blueberry ingestion on natural killer cell counts, oxidative stress, and inflammation prior to and after 2.5 h of running. Appl Physio Nutr Metab, 36(6), 976-84. DOI:10.1139/h11-120

Panickar, K.S., & Anderson, R.A. (2010). Role of dietary polyphenols in attenuating brain edema and cell swelling in cerebral ischemia. Recent Pat CNS Drug Discov, 5(2), 99-108. DOI: https://doi.org/10.2174/157488910791213149

Youdim, K.A., McDonald, J., Kalt, W., Joseph, J.A. (2002). Potential role of dietary flavonoids in reducing microvascular endothelium vulnerability to oxidative and inflammatory insults. J. Nutr. Biochem, 13(5), 282-288. http://doi.org/10.1016/S0955-2863(01)00221-2

BLUEBERRY AND HEART HEALTH

Erlund, I., Koli, R., Alfthan, G., Marniemi, J., Puukka, P., Mustonen, P… Jula, A. (2008). Favorable effects of berry consumption on platelet function, blood pressure, and HDL cholesterol. Am J Clin Nutr 87, 323-331. Article

Louis, X.L., Thandapilly, S.J., Kalt, W., Vinqvist-Tymchuk, M., Aloud, B.M, Raj, P., … Netticadan, T. (2014). Blueberry polyphenols prevent cardiomyocyte death by preventing calpain activation and oxidative stress. Food Funct, 5(8), 1785-94. DOI:10.1039/c3fo60588d

McAnulty, L.S., Collier, S.R., Landram, M.J., Whittaker, D.S., Isaacs, S.E., Klemka, J.M… McAnulty, S.R. (2014). Six weeks daily ingestion of whole blueberry powder increases natural killer cell counts and reduces arterial stiffness in sedentary males and females. Nutr Res, 34 (7), 577-84. DOI: 10.1016/j.nutres.2014.07.002

McAnulty, S.R., McAnulty, L.S., Morrow, J.D., Khardouni, D., Shooter, L., Monk, J., Gross, S., Brown, V. (2005). Effect of daily fruit ingestion on converting enzyme activity, blood pressure, and oxidative stress in chronic smokers. Free Radic Res, 39(11),1241-8. DOI: 10.1080/10715760500306836

BIOAVAILABILITY OF ANTHOCYANIN FOR HEALTH

Bell, L., Lamport, D.J., Butler, L.T., & Williams, C.M. (2015).A Review of the Cognitive Effects Observed in Humans Following Acute Supplementation with Flavonoids, and Their Associated Mechanisms of Action. Nutrients, 7(12), 10290-10306. doi: 10.3390/nu7125538

Lila, M.A., Burton-Freeman, B., Grace, M., & Kalt, W. (2016). Unraveling Anthocyanin Bioavailability for Human Health. Annu Rev Food Sci Technol,7, 375-93. DOI: 10.1146/annurev-food-041715-033346

Mazza, G., Kay, C.D., Cottrell, T., & Holub, B.J. (2002). Absorption of Anthocyanins from Blueberries and Serum Antioxidant Status in Human Subjects. J. Agric. Food Chem, 50(26), 7731-7737. http://pubs.acs.org/doi/abs/10.1021/jf020690l

Sandhu, A.K., Huang, Y., Xiao, D., Par, E., Edirisinghe, I., & Burton-Freeman, B. (2016). Pharmacokinetic Characterization and Bioavailability of Strawberry Anthocyanins Relative to Meal Intake. J Agric Food Chem, 64(24), 4891-9. DOI:10.1021/acs.jafc.6b00805

One Vegetarian Capsule Contains: 

Blueberry (Vaccinium corymbosum) Freeze-dried Extract (80:1)  500mg 
  Anthocyanins 12% Typical 
  Polyphenos 40% Minimum 
  Chlorogeninc Acid 5% Minimum 
  ORAC units per gram 6500 

Typical Other Ingredients cellulose & water (capsule shell)

BLUEBERRY EXTRACT — Designed to support the regeneration of the brain and nervous system

Brain health: Take 1 capsule a day for regeneration of brain and nerve cells.*

Cognitive and memory: Take 1 capsule a day. Add 1 cap High ORAC.  Students: Take 1-2 caps of both the Blueberry Extract and the High ORAC a day.*

Foggy brain: Take 2 capsules for a month then 1 cap a day as maintenance.*

Neural regeneration: Take 1-2 capsules a day. Add Phyto Power and/or No 7 for broad-spectrum phenolic support.*

Anti-inflammation: Due to the high concentration of anthocyanins (80 pounds produce 1 pound of the extract), the Blueberry Extract is excellent as anti-inflammatory agent. Reduces C-reactive protein (inflammatory marker), Isoprostane (marker for lipid oxidation), and NF-Kß (global inflammatory marker) for brain, heart, and DNA health.* 

Our Favorite: When our president, Dr. Dohrea Bardell, went through her PhD program, for six years she took 2 capsules of the Blueberry Extract every day to keep her brain active and agile. She worked 12 hours days researching and writing. When she presented papers at conventions, she often added the Phyto Power for extra boost. The Blueberry Extract is one of her most favorite products.*

Description 

The Blueberry Extract offers the highest concentration of the North American blueberry species, Vaccinium corymbosum, with a significant broad-spectrum phenolic profile.

The Blueberry Extract is a powerful concentration of anthocyanins: It takes eighty pounds of blueberries to get one pound of the pure purple extract. This means that one capsule of the extract is equivalent to a cup and a quarter of whole blueberries.

Each vegan capsule has 500mg of the pure extract, without any excipients or fillers.

Tuft University’s James Joseph and Barbara Shukitt-Hale have researched the use and application of blueberries as a potential therapeutic agent for many years. Their studies along with their colleagues demonstrate that blueberries and blueberry extract reverse and prevent brain aging (Shukitt-Hale et al., 2008; 2007), improve memory and motor skills (Carey et al., 2014; Malin et al., 2011; Brewer et al., 2010), repair neuronal tissue and function (Joseph et al., 2003; Miller et al., 2012), and serve as a potent anti-aging food (Joseph et al., 1999; 2009; Shukitt-Hale et al., 2015; 2012).*

The Blueberry Extract was designed with Dr. Joseph’s assistance by converting some of the data from his research to human consumption.*

Steward, Sridhar, and Meyer (2013) define regeneration of the nerves as a process of repairing or replacing nerve cells that have been damaged. Studies have hypothesized that an antioxidant-enriched diet may affect neuro-regeneration and inhibit inflammation due to their high anthocyanins (Szajdek & Borowska, 2008; Sweeney et al., 2002).*

Research studies and reviews by Latif (2015), Panickar & Anderson (2010), Subash et al. (2014), Panickar (2013), Schaffer et al. (2006), and Letenneur et al. (2007), demonstrate the great ability of flavonoids to offer a consistent neuro-protective nutriceutical.

Stratheam et al. (2014) demonstrate that anthocyanin rich extracts of blueberries and grape seed support the process of neuro re-generation by interfering with the neurotoxin, rotenone, and improving the mitochondrial function. Gao et al. (2012) find that a habitual intake of dietary flavonoids is associated with a lower risk of developing neurological issues, such as Parkinson, or lessening brain edema (Panickar & Anderson, 2010). Kovacsova et al. (2010) researched the biochemical pathways and molecular neuro-protective mechanisms of polyphenols in the brain. Antioxidant activity reduces neuro-inflammation and supports the prevention of neuro-degeneration (Stromberg et al., 2005). Williams & Spencer (2012) and Galli et al. (2006) show that a blueberry-supplemented diet reverses age-related declines with improved cognition and nerve regeneration.*

The process of neurological regenerative ability of blueberries is linked to their potent anti-inflammatory and antioxidant properties (Subash et al., 2014; Duffy et al., 2008; Shukitt-Hale et al., 2008), effecting the reduction of NF Kappa beta, Cox-2 and Isoprostane (Youdim et al., 2002). For this reason, studies emphasize the important dietary role of blueberries, as anthocyanins are able to reduce oxidative stress and anti-inflammatory cytokines (McAnulty et al., 2011).*

Due to their high levels of anthocyanins, blueberries are also shown in research to contribute to heart health (McAnulty, 2014; Louis et al., 2014; Erlund et al., 2008; Youdim & Joseph, 2001).*

How available are these anthocyanins? Mazza et al. (2002) has demonstrated that consumption of blueberries raises blood serum ORAC (antioxidant capacity). Emerging evidence confirms the ability of the human body to absorb anthocyanins, demonstrating a greater bioavailability (Bell et al., 2015), prolonged circulation, and relatively high concentration of anthocyanins metabolites (Lila et al., 2016).*

See the Research tab for additional bibliography to further understand the application and use of blueberry and blueberry extract.

*These statements have not been evaluated by the Food & Drug Administration. This products is not intended to diagnose, treat, cure or prevent any disease. The information and citations of research are for informational purposes only. Please be sure to consult your health care provider before taking this or any other product.

REFERENCES

Erlund, I., Koli, R., Alfthan, G., Marniemi, J., Puukka, P., Mustonen, P… Jula, A. (2008). Favorable effects of berry consumption on platelet function, blood pressure, and HDL cholesterol. Am J Clin Nutr 87, 323-331. Article

Galli, R.L., Bielinski, D.F., Szprengiel, A., Shukitt-Hale, B., Joseph, J.A. (2006). Blueberry supplemented diet reverses age-related decline in hippocampal HSP70 neuroprotection. Neurobio Aging, 27, 344-350. DOI:10.1016/j.neurobiolaging.2005.01.017

Gao, X., Cassidy, A., Schwarzschild, M.A., Rimm, E.B., & Ascherio, A. (2012). Habitual intake of dietary flavonoids and risk of Parkinson disease. Neurology, 78(10), 1138-45. doi: 10.1212/WNL.0b013e31824f7fc4

Joseph, J., Cole, G., Head, E., Ingram, D. (2009). Nutrition, brain aging, and neurodegeneration. J. Neurosci. 29(41), 12795–12801. DOI: 10.1523/JNEUROSCI.3520-09.2009

Joseph, J.A., Shukitt-Hale, B., & Lau, F.C. (2007). Fruit polyphenols and their effects on neuronal signaling and behavior in senescence . Ann NY Acd Sci, 1100, 470-85. DOI: 10.1196/annals.1395.052

Joseph, J.A., Denisova, N.A., Arendash, G., Gordon, M., Diamond, D., Shukitt-Hale, B., Morgan, D. (2003). Blueberry supplementation enhances signaling and prevents behavioral deficits in an Alzheimer disease model. Nutr Neurosci, 6 (3), 153-162. DOI:10.1080/1028415031000111282

Joseph, J.A., Shukitt-Hale, B., Denisova, N.A., Bielinski, D., Martin, A., McEwen, J.J., & Bickford, P.C. (1999). Reversals of age-related declines in neuronal signal

Joseph, J., Cole, G., Head, E., Ingram, D. (2009). Nutrition, brain aging, and neurodegeneration. J. Neurosci. 29(41), 12795–12801. DOI: 10.1523/JNEUROSCI.3520-09.2009

Kovacsova, M., Barta, A., Parohova, J., Vrankova, S., Pechanova, O. (2010). Neuroprotective mechanisms of natural polyphenolic compounds. Act Nerv Super Rediviva, 52, 181-186. Abstract

Latif, R. (2015). Flavonoids as novel neuroprotective nutraceuticals. Saudi J Health Sci, 4, 1-4. DOI:10.4103/2278-0521.151402

McAnulty, L.S. Nieman, D.C., Dumke, C.L., Shooter, L.A., Henson, D.A., Utter, A.C., … McAnulty, S.R. (2011). Effect of blueberry ingestion on natural killer cell counts, oxidative stress, and inflammation prior to and after 2.5 h of running. Appl Physio Nutr Metab, 36(6), 976-84. DOI:10.1139/h11-120

Panickar, K.S., & Jang, S. (2013). Dietary and plant polyphenols exert neuroprotective effects and improve cognitive function in cerebral ischemia. Recent Pat Food Nutr Agric, 5(2), 128-43. DOI: 10.2174/1876142911305020003

Schaffer, S., Eckert, G.P., Schmitt-Schilling, S., & Muller, W.E. (2006). Plant foods and brain aging: a critical appraisal.Forum Nutr, 59, 86-115. DOI: 10.1159/000095209

Shukitt-Hale, B., Bielinski, D.F., Lau, F.C., Willis, L.M., Carey, A.N., & Joseph, J.A. (2015). The beneficial effects of berries on cognition, motor behaviour and neuronal function in ageing. Br J Nutr, 114 (10), 1542-9.DOI: 10.1017/S0007114515003451

Shukitt-Hale, B. (2012). Blueberries and neuronal aging.Gerontology, 58, 518-523. DOI: 10.1159/000341101

Shukitt-Hale, B., Lau, F.C., Joseph, J.A. (2008). Berry fruit supplementation and the aging brain. Journal of Agricultural and Food Chemistry, 56, 636–641. DOI10.1021/jf072505f

Shukitt-Hale, B., Carey, A.N., Jenkins, D., Rabin, B.M., Joseph, J.A. (2007). Beneficial effects of fruit extracts on neuronal function and behavior in a rodent model of accelerated aging. Neurobiol Aging, 28, 1187-1194. DOI: 10.1016/j.neurobiolaging.2006.05.031

Steward, M.N., Sridhar, A., & Meyer, J.S. (2013). Neural regeneration. Curr Top Microbiol Immunol, 367, 163-91. DOI: 10.1007/82_2012_302.

Strathearm, K.D., Yousef, G.G., Grace, M.H., Tambe, M.A., Ferruzzi, M.G., Wu, Q.L., Simon, J.E., Lila, M.A., & Rochet, J.C. (2014). Neuroprotective effects of anthocyanin-and proanthocyanidin-rich extracts in cellular models of Parkinson’s diseases. Brain Res, 1555, 60-77. . DOI: 10.1016/j.brainres.2014.01.047

Subash, S., Essa, M.M., Al-Adwi, S., Memon, M.A., Manivasagan, T., & Akbar, M. (2014). Neuroprotective effects of berry fruits on neurodegenerative diseases. Neural Regeneration Research, 9(16), 1557-1566. . DOI:10.4103/1673-5374.139483

Sweeney, M.I., Kalt, W., MacKinnon, S.L., Ashby, J., Gottschall-Pass, K.T. (2002) Feeding rats diets enriched in lowbush blueberries for six weeks decreases ischemia-induced brain damage. Nutr Neurosci 5, 427- 431. DOI: 10.1080/1028415021000055970

Youdim, K.A., Joseph, J.A. (2001). A possible emerging role of phytochemicals in improving age-related neurological dysfunctions: a multiplicity of effects. Free Radic Biol Med, 30, 583-594. http://doi.org/10.1016/S0891-5849(00)00510-4

Research

FOOD SCIENCE: THE APPLICATION AND USE OF BLUEBERRY AND BLUEBERRY EXTRACT.*

Blueberry and Cognitive Support

Brewer, G.J., Torricelli, J.R., Lindsey, A.L., Kunz, E.Z., Neuman, A., Fisher, D.R., & Joseph, J.A. (2010). Age-related toxicity of amyloid-beta associated with increased pERK and pCREB in primary hippocampal neurons: reversal by blueberry extract. J Nutr Biochem, 21, 991-998. DOI: 10.1016/j.jnutbio.2009.08.005

Carey, A.N., Gomes, S.M., & Shukitt-Hale, B. (2014). Blueberry supplementation improves memory in middle-aged mice fed a high-fat diet. J Agric Food Chem, 62, 3972-3978. DOI: 10.1021/jf404565s

Casadesus, G., Shukitt-Hale, B., Stellwagen, H.M., Zhu, X., Lee, H.G., Smith, M.A., Joseph, J.A. (2004). Modulation of hippocampal plasticity and cognitive behavior by short-term blueberry supplementation in aged rats. Nutr Neurosci, 7, 309-316. DOI:10.1080/10284150400020482

Chemiack, E.P. (2012). A berry thought-provoking idea: the potential role of plant polyphenols in the treatment of age-related cognitive disorder. Br J Nutr, 108(5), 794-800. DOI: 10.1017/S0007114512000669

Devore, E.E., Kang, J.H., Breteler, M.M., & Grodstein, F. (2012). Dietary intakes of berries and flavonoids in relation to cognitive decline. Ann Neurol, 72(1), 135-43. DOI:10.1002/ana.23594

Duffy, K.B., Spangler, E.L., Devan, B.D., Guo, Z., Bowker, J.L., Janas, A.M., Hagepanos, A., Minor, R.K., DeCabo, R., Mouton, P.R., Shukitt-Hale, B., Joseph, J.A., Ingram, D.K. (2008). A blueberry-enriched diet provides cellular protection against oxidative stress and reduces a kainate-induced learning impairment in rats. Neurobiol Aging, 29, 1680-1689. DOI: 10.1016/j.neurobiolaging.2007.04.002

Goyarzu, P., Malin, D.H., Lau, F.C., Taglialatela, G., Moon, W.D., Jennings, R., Moy, E., Moy, D., Lippold, S., Shukitt-Hale, B., Joseph, J.A. (2004). Blueberry supplemented diet: effects on object recognition memory and nuclear factor-kappa B levels in aged rats. Nutr Neurosci, 7, 75-83. DOI: 10.1080/10284150410001710410

Joseph, J.A., Shukitt-Hale, B., & Lau, F.C. (2007). Fruit polyphenols and their effects on neuronal signaling and behavior in senescence . Ann NY Acd Sci, 1100, 470-85. DOI: 10.1196/annals.1395.052

Joseph, J.A., Shukitt-Hale, B., Denisova, N.A., Bielinski, D., Martin, A., McEwen, J.J., & Bickford, P.C. (1999). Reversals of age-related declines in neuronal signal transduction, cognitive, and motor behavioral deficits with blueberry, spinach, or strawberry dietary supplementation. J Neurosci, 19(18), 8114-21. . Article

Krikorian, R., Shidler, M.D., Nash, T.A., Kalt, W., Vingvist-tymchuk, M.R., Shukitt-Hale, B., Joseph, J.A. (2010). Blueberry supplementation improves memory in older adults. J. Agric Food Chem, 58, 3996-4000. DOI: 10.1021/jf9029332

Letennuur, L., Proust-Lima, C., Le Gouge, A., Dartigues, J.F., & Barberger-Gateau, P. (2007). Flavonoid intake and cognitive decline over a 10-year period. Am J Epideminol, 165(12), 1364-71. DOI: 10.1093/aje/kwm036

Malin, D.H., Lee, D.R., Goyarzum P., Chang, Y.H., Ennis, L.J., Beckett, E., Shukitt-Hale, B., Joseph, J.A. (2011). Short-term blueberry-enriched diet prevents and reverses object recognition memory loss in aging rats. Nutrition, 27, 338-342. DOI: 10.1016/j.nut.2010.05.001

Poulose, S.M., carey, A.N., Shukitt-Hale, B. (2012). Improving brain signaling in aging: Could berries be the answer?Expert Rev Neurother, 12(8), 887-9. DOI: 10.1586/ern.12.86

Rendeiro, C., Vauzour, D., Rattray, M., Waffo-Téguo, P., Mérillon, J.M., Butler, L.T., Williams, C.M., & Spencer, J.P. (2013). Dietary levels of pure flavonoids improve spatial memory performance and increase hippocampal brain-derived neurotrophic factor. PLoS One, 8(5), e63535. DOI: 10.1371/journal.pone.0063535

Rendeiro, C., Vauzour, D., Kean, R.J., Butler, L.T., Rattray, M., Spencer, J.P., & Williams, C.M. (2012). Blueberry supplementation induces spatial memory improvements and region-specific regulation of hippocampal BDNF mRNA expression in young rats. Psychopharmacology (Berl), 223 (3), 319-30. DOI: 10.1007/s00213-012-2719-8 .

Rendeiro, C., Guerreiro, J.D., Williams, C.M., Spencer, J.P. (2012). Flavonoids as modulators of memory and learning: molecular interactions resulting in behavioural effects. Proc Nutr Soc, 71(2), 246-62. DOI: 10.1017/S0029665112000146

Schaffer, S., Eckert, G.P., Schmitt-Schilling, S., & Muller, W.E. (2006). Plant foods and brain aging: a critical appraisal. Forum Nutr, 59, 86-115. DOI: 10.1159/000095209

Shukitt-Hale, B., Bielinski, D.F., Lau, F.C., Willis, L.M., Carey, A.N., & Joseph, J.A. (2015). The beneficial effects of berries on cognition, motor behaviour and neuronal function in ageing. Br J Nutr, 114 (10), 1542-9.DOI: 10.1017/S0007114515003451

Shukitt-Hale, B. (2012). Blueberries and neuronal aging. Gerontology, 58, 518-523. DOI: 10.1159/000341101

Shukitt-Hale, B., Lau, F.C., Joseph, J.A. (2008). Berry fruit supplementation and the aging brain. Journal of Agricultural and Food Chemistry, 56, 636–641. DOI:10.1021/jf072505f

Spencer, J.P. (2010). The impact of fruit flavonoids on memory and cognition. Br J Nutr, 104(3), S40-7. DOI: 10.1017/S0007114510003934

Vauzour, D. (2014). Effect of flavonoids on learning, memory and neurocognitive performance: relevance and potential implications for Alzheimer's disease pathophysiology. J Sci Food Agric, 94(6), 1042-56. DOI: 10.1002/jsfa.6473

Willis, L.M., Shukitt-Hale, B., Joseph, J.A. (2009). Recent advances in berry supplementation and age-related cognitive decline. Curr Opin Clin Nutr Metab Care, 12(1), 91-4. DOI: 10.1097/MCO.0b013e32831b9c6e

BLUEBERRY AND NEURO-PROTECTIVE EFFECT

Baptista, F.I., Henriques, A.G., Silva, A.M., Wiltfang, J., & da Cruz e Silva, O.A. (2014). Flavonoids as therapeutic compounds targeting key proteins involved in Alzheimer's disease. ACS Chem Neurosci, 5(2), 83-92. DOI: 10.1021/cn400213r

Campos-Esparza, M.R., & Torres-Ramos, M.A. (2010). Neuroprotection by natural polyphenols: molecular mechanisms. Cent Nerv Syste Agents Med Chem, 10(4), 269-77. DOI: 10.2174/187152410793429728

Esposito, E., Rotilio, D., Di Matteo, V., Di Giulio, C., Cacchio, M., Algeri, S. (2012). A review of specific dietary antioxidants and the effects on biochemical mechanisms related to neurodegenerative processes. Neurobiol Aging, 23, 719-735.

http://doi.org/10.1016/S0197-4580(02)00078-7

Galli, R.L., Bielinski, D.F., Szprengiel, A., Shukitt-Hale, B., Joseph, J.A. (2006). Blueberry supplemented diet reverses age-related decline in hippocampal HSP70 neuroprotection. Neurobio Aging, 27, 344-350. DOI:

10.1016/j.neurobiolaging.2005.01.017

Gao, X., Cassidy, A., Schwarzschild, M.A., Rimm, E.B., & Ascherio, A. (2012). Habitual intake of dietary flavonoids and risk of Parkinson disease. Neurology, 78(10), 1138-45. doi: 10.1212/WNL.0b013e31824f7fc4

Giacalone, M., Di Sacco, F. Traupe, I., Topini, R., Forfori, F., & Giunta, F. (2011). Antioxidant and neuroprotective properties of blueberry polyphenols: A critical review. Nutr Neurosci, 14(3), 119-25. DOI: 10.1179/1476830511Y.0000000007

Fuentealba, J., Dibarrant, A.J., Fuentes-Fuentes, M.C., Saez-Orellana, F., Qunones, K., Guzman, L., … Aguayo, L.G. (2011). Syaptic failure and adenosine triphosphate imbalance induced by amyloid-β aggregates are prevented by blueberry-enriched polyphenols extracts. J Neurosci Res, 89(9), 1499-508. DOI: 10.1002/jnr.22679

Joseph, J., Cole, G., Head, E., Ingram, D. (2009). Nutrition, brain aging, and neurodegeneration. J. Neurosci. 29(41), 12795–12801. DOI: 10.1523/JNEUROSCI.3520-09.2009

Joseph, J.A., Denisova, N.A., Arendash, G., Gordon, M., Diamond, D., Shukitt-Hale, B., Morgan, D. (2003). Blueberry supplementation enhances signaling and prevents behavioral deficits in an Alzheimer disease model. Nutr Neurosci, 6 (3), 153-162. DOI:

10.1080/1028415031000111282

Joseph, J.A., Shukitt-Hale, B., Denisova, N.A., Bielinski, D., Martin, A., McEwen, J.J., Bickford, P.C. (1999). Reversals of age-related declines in neuronal signal transduction, cognitive, and motor behavioral deficits with blueberry, spinach, or strawberry dietary supplementation. J Neurosci 19, 8114-8121. Article

Kolosova, N.G., Shcheglova, T.V., Sergeeva, S.V., Loskutova, L.V. (2006) Long-term antioxidant supplementation attenuates oxidative stress markers and cognitive deficits in senescent-accelerated OXYS rats. Neurobiol Aging, 27, 1289-1297. DOI:10.1016/j.neurobiolaging.2005.07.022

Kovacsova, M., Barta, A., Parohova, J., Vrankova, S., Pechanova, O. (2010). Neuroprotective mechanisms of natural polyphenolic compounds. Act Nerv Super Rediviva, 52, 181-186. Abstract

Latif, R. (2015). Flavonoids as novel neuroprotective nutraceuticals. Saudi J Health Sci, 4, 1-4. DOI:10.4103/2278-0521.151402

Meng, X., Munishkina, L.A., Fink, A.L., Uversky, V.N. (2010). Effects of Various Flavonoids on the α-Synuclein Fibrillation Process. Parkinson Dis., 650794. DOI:10.4061/2010/650794

Miller, M.G., Shukitt-Hale, B. (2012). Berry fruit enhances beneficial signaling in the brain. J. Agric. Food Chem, 60(23), 5709–5715. DOI: 10.1021/jf2036033

Nile, S.H., Park, S.W. (2014). Edible berries: Bioactive components and their effect on human health. Nutrition, 30, 134-144. DOI: 10.1016/j.nut.2013.04.007

Ono, K., Yoshiike, Y., Takashima, A., Hasegawa, K., Naiki, H., & Ymada, M. (2003). Potent Anti-amyloidogenic and fibril-destabilizing effects of polyphenols in vitro: Implications for the prevention and therapeutics of Alzheimer’s isease. J Neurochem, 87, 172-181. . DOI:10.1046/j.1471-4159.2003.01976.x

Pandey, K.B., Rizv,i S.I. (2009). Plant polyphenols as dietary antioxidants in human health and disease. Oxid Med Cell Longev, 2, 270-278. doi: 10.4161/oxim.2.5.9498

Panickar, K.S., & Jang, S. (2013). Dietary and plant polyphenols exert neuroprotective effects and improve cognitive function in cerebral ischemia. Recent Pat Food Nutr Agric, 5(2), 128-43. DOI: 10.2174/1876142911305020003

Schaffer, S., Eckert, G.P., Schmitt-Schillig, S., Müller, W.E. (2006). Plant foods and brain aging: a critical appraisal. Forum Nutr, 59, 86-115. DOI: 10.1159/000095209

Schroeter, H., Boyd, C., Spencer, J.P., Williams, R.J., Cadenas, E., Rice-Evans, C. (2002). MAPK signaling in neurodegeneration: influences of flavonoids and of nitric oxide. Neurobiol Aging 23(5), 861–880. DOI: http://dx.doi.org/10.1016/S0197-4580(02)00075-1

Shukitt-Hale, B. (2012). Blueberries and neuronal aging. Gerontology, 58(6), 518-23. DOI: 10.1159/000341101.

Shukitt-Hale, B., Lau, F.C., Carey, A.N., Galli, R.L., Spangler, E.L., Ingram, D.K., Joseph, J.A. (2008). Blueberry polyphenols attenuate kainic acid-induced decrements in cognition and alter inflammatory gene expression in rat hippocampus. Nutr Neurosci, 11, 172-182. DOI: 10.1179/147683008X301487

Shukitt-Hale, B., Carey, A.N., Jenkins, D., Rabin, B.M., Joseph, J.A. (2007). Beneficial effects of fruit extracts on neuronal function and behavior in a rodent model of accelerated aging. Neurobiol Aging, 28, 1187-1194. DOI: 10.1016/j.neurobiolaging.2006.05.031

Spencer, J.P. (2010). Beyond antioxidants: the cellular and molecular interactions of flavonoids and how these underpin their actions on the brain. Proc Nutr Soc, 69(2):244-60. DOI: 10.1017/S0029665110000054

Spencer, J.P., Vauzour, D., Rendeiro, C. (2009). Flavonoids and cognition: the molecular mechanisms underlying their behavioural effects. Arch Biochem Biophys, 492(1-2):1-9 DOI: 10.1017/S0029665112000146

Steward, M.N., Sridhar, A., & Meyer, J.S. (2013). Neural regeneration. Curr Top Microbiol Immunol, 367, 163-91. DOI: 10.1007/82_2012_302

Strathearm, K.D., Yousef, G.G., Grace, M.H., Tambe, M.A., Ferruzzi, M.G., Wu, Q.L., Simon, J.E., Lila, M.A., & Rochet, J.C. (2014). Neuroprotective effects of anthocyanin-and proanthocyanidin-rich extracts in cellular models of Parkinson’s diseases. Brain Res, 1555, 60-77. . DOI: 10.1016/j.brainres.2014.01.047

Stromberg, I., Gemma, C., Vila, J., Bickford, P.C. (2005). Blueberry- and spirulina-enriched diets enhance striatal dopamine recovery and induce a rapid, transient microglia activation after injury of the rat nigrostriatal dopamine system. Exp Neurol, 196, 298-307. DOI: 10.1016/j.expneurol.2005.08.013

Subash, S., Essa, M.M., Al-Adwi, S., Memon, M.A., Manivasagan, T., & Akbar, M. (2014). Neuroprotective effects of berry fruits on neurodegenerative diseases. Neural Regeneration Research, 9(16), 1557-1566. . DOI:10.4103/1673-5374.139483

Sweeney, M.I., Kalt, W., MacKinnon, S.L., Ashby, J., Gottschall-Pass, K.T. (2002) Feeding rats diets enriched in lowbush blueberries for six weeks decreases ischemia-induced brain damage. Nutr Neurosci 5, 427- 431. DOI: 10.1080/1028415021000055970

Szajdek, A., Borowska, J.E. (2008). Bioactive compounds and health-promoting properties of berry fruits a review. Plant Foods Hum Nutr, 63,147-156. DOI:10.1007/s11130-008-0097-5

Wang, Y., Chang, C.F., Chou, J., Chen, H.L., Deng, X., Harvey, B.K., Cadet, J.L., Bickford, P.C. (2005). Dietary supplementation with blueberries, spinach, or spirulina reduces ischemic brain damage. Exp Neurol, 193, 75-84. DOI: 10.1016/j.expneurol.2004.12.014

Williams, C.M., El Mohsen, M.A., Vauzour, D., Rendeiro, C., Butler, L.T., Ellis, J.A., Whiteman, M., Spencer, J.P. (2008). Blueberry induced changes in spatial working memory correlate with changes in hippocampal CREB phosphorylation and brain-derived neurotrophic factor (BDNF) levels. Free Radical Biol Med, 45, 295-305. DOI:10.1016/j.freeradbiomed.2008.04.008

Williams, R.J. & Spencer, J.P. (2012). Flavonoids, cognition, and dementia: actions, mechanisms, and potential therapeutic utility for Alzheimer disease. Free Radic Biol Med, 52(1), 35-45. DOI: 10.1016/j.freeradbiomed.2011.09.010

Youdim, K.A., Joseph, J.A. (2001). A possible emerging role of phytochemicals in improving age-related neurological dysfunctions: a multiplicity of effects. Free Radic Biol Med, 30, 583-594. http://doi.org/10.1016/S0891-5849(00)00510-4

Youdim, K.A., Shukitt-Hale, B., Martin, A., Wang, H., Denisova, N., Bickford, P.C., Joseph, J.A. (2000). Short-term dietary supplementation of blueberry polyphenolics: beneficial effects on aging brain performance and peripheral tissue function. Nutr Neurosci, 3, 383-397. http://dx.doi.org/10.1080/1028415X.2000.11747338

SYSTEMIC ANTI-INFLAMMATORY SUPPORT

Akiyama et al. (2000). Inflammation and Alzheimer’s disease. Neurobiol Aging, 21(3), 383-421. doi: 10.1101/cshperspect.a006346

Grace, M.H., Esposito D., Dunlap K.L., & Lila M.A. (2014). Comparative analysis of phenolic content and profile, antioxidant capacity, and anti-inflammatory bioactivity in wild Alaskan and commercial Vaccinium berries. J Agric Food Chem, 62(18), 4007-17. doi: 10.1021/jf403810y.

McAnulty, L.S. Nieman, D.C., Dumke, C.L., Shooter, L.A., Henson, D.A., Utter, A.C., … McAnulty, S.R. (2011). Effect of blueberry ingestion on natural killer cell counts, oxidative stress, and inflammation prior to and after 2.5 h of running. Appl Physio Nutr Metab, 36(6), 976-84. DOI:10.1139/h11-120

Panickar, K.S., & Anderson, R.A. (2010). Role of dietary polyphenols in attenuating brain edema and cell swelling in cerebral ischemia. Recent Pat CNS Drug Discov, 5(2), 99-108. DOI: https://doi.org/10.2174/157488910791213149

Youdim, K.A., McDonald, J., Kalt, W., Joseph, J.A. (2002). Potential role of dietary flavonoids in reducing microvascular endothelium vulnerability to oxidative and inflammatory insults. J. Nutr. Biochem, 13(5), 282-288. http://doi.org/10.1016/S0955-2863(01)00221-2

BLUEBERRY AND HEART HEALTH

Erlund, I., Koli, R., Alfthan, G., Marniemi, J., Puukka, P., Mustonen, P… Jula, A. (2008). Favorable effects of berry consumption on platelet function, blood pressure, and HDL cholesterol. Am J Clin Nutr 87, 323-331. Article

Louis, X.L., Thandapilly, S.J., Kalt, W., Vinqvist-Tymchuk, M., Aloud, B.M, Raj, P., … Netticadan, T. (2014). Blueberry polyphenols prevent cardiomyocyte death by preventing calpain activation and oxidative stress. Food Funct, 5(8), 1785-94. DOI:10.1039/c3fo60588d

McAnulty, L.S., Collier, S.R., Landram, M.J., Whittaker, D.S., Isaacs, S.E., Klemka, J.M… McAnulty, S.R. (2014). Six weeks daily ingestion of whole blueberry powder increases natural killer cell counts and reduces arterial stiffness in sedentary males and females. Nutr Res, 34 (7), 577-84. DOI: 10.1016/j.nutres.2014.07.002

McAnulty, S.R., McAnulty, L.S., Morrow, J.D., Khardouni, D., Shooter, L., Monk, J., Gross, S., Brown, V. (2005). Effect of daily fruit ingestion on converting enzyme activity, blood pressure, and oxidative stress in chronic smokers. Free Radic Res, 39(11),1241-8. DOI: 10.1080/10715760500306836

BIOAVAILABILITY OF ANTHOCYANIN FOR HEALTH

Bell, L., Lamport, D.J., Butler, L.T., & Williams, C.M. (2015).A Review of the Cognitive Effects Observed in Humans Following Acute Supplementation with Flavonoids, and Their Associated Mechanisms of Action. Nutrients, 7(12), 10290-10306. doi: 10.3390/nu7125538

Lila, M.A., Burton-Freeman, B., Grace, M., & Kalt, W. (2016). Unraveling Anthocyanin Bioavailability for Human Health. Annu Rev Food Sci Technol,7, 375-93. DOI: 10.1146/annurev-food-041715-033346

Mazza, G., Kay, C.D., Cottrell, T., & Holub, B.J. (2002). Absorption of Anthocyanins from Blueberries and Serum Antioxidant Status in Human Subjects. J. Agric. Food Chem, 50(26), 7731-7737. http://pubs.acs.org/doi/abs/10.1021/jf020690l

Sandhu, A.K., Huang, Y., Xiao, D., Par, E., Edirisinghe, I., & Burton-Freeman, B. (2016). Pharmacokinetic Characterization and Bioavailability of Strawberry Anthocyanins Relative to Meal Intake. J Agric Food Chem, 64(24), 4891-9. DOI:10.1021/acs.jafc.6b00805

Ingredients 

One Vegetarian Capsule Contains: 

Blueberry (Vaccinium corymbosum) Freeze-dried Extract (80:1)  500mg 
  Anthocyanins 12% Typical 
  Polyphenos 40% Minimum 
  Chlorogeninc Acid 5% Minimum 
  ORAC units per gram 6500 

Typical Other Ingredients cellulose & water (capsule shell)

Protocol

BLUEBERRY EXTRACT — Designed to support the regeneration of the brain and nervous system

Brain health: Take 1 capsule a day for regeneration of brain and nerve cells.*

Cognitive and memory: Take 1 capsule a day. Add 1 cap High ORAC.  Students: Take 1-2 caps of both the Blueberry Extract and the High ORAC a day.*

Foggy brain: Take 2 capsules for a month then 1 cap a day as maintenance.*

Neural regeneration: Take 1-2 capsules a day. Add Phyto Power and/or No 7 for broad-spectrum phenolic support.*

Anti-inflammation: Due to the high concentration of anthocyanins (80 pounds produce 1 pound of the extract), the Blueberry Extract is excellent as anti-inflammatory agent. Reduces C-reactive protein (inflammatory marker), Isoprostane (marker for lipid oxidation), and NF-Kß (global inflammatory marker) for brain, heart, and DNA health.* 

Our Favorite: When our president, Dr. Dohrea Bardell, went through her PhD program, for six years she took 2 capsules of the Blueberry Extract every day to keep her brain active and agile. She worked 12 hours days researching and writing. When she presented papers at conventions, she often added the Phyto Power for extra boost. The Blueberry Extract is one of her most favorite products.*

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