Monday, May 16, 2011

Wild Blueberry Supports Brain Function

Oxidative stress and inflammation are toxic to neurons and can lead to the death of brain cells. Since this occurs more often in the brain of someone with T21--and is reported to happen even before birth-- a good antioxidant is important to use. Fortunately, blueberries are one of the most powerful antioxidants for enhancing memory and preserving brain function. In fact, juice made from wild blueberries may reduce oxidative damage to DNA by around 3%, according to a recent study. (See "Effect of wild blueberry..." below.) 

It's the blueberry's anthocyanins (the pigments giving the blue color) that are capable of crossing the blood-brain-barrier and become localized in the memory and learning centers of the brain (including the hippocampus, cerebellum and cortex). This action is important because we'd like the benefits to occur in the brain.

In the 2010 publication, Blueberry supplementation attenuates microglial activation in hippocampal intraocular grafts to aged hosts, it was found that the glial cells (the "bad cells" for those with DS because they kill too many brain cells) had decreased activity with blueberry supplementation. Since the blueberries stopped the glial cell activity, there were more surviving neurons (the "good cells").

To learn more about the effects of blueberries on the brain, please see the blog post Back to Blueberries from the Anti-Aging Firewall.

Benefits Overview
  • Memory Enhancement. Blueberry facilitates neurogenesis (the creation of new neurons) in the hippocampus (memory) region of the brain. The hippocampus is the area responsible for short-term memory. This study (see study entitled "NT-020..." below) focused on blueberry supplemented diets of aged rats. The study found a direct correlation between the increase in proliferation of new neurons and the ability of the aged rats to perform in maze navigation studies.
  • Better control of body movements. Aged research rats fed blueberry extract were found to have higher levels of brain neurotransmitter dopamine. Dopamine is the chemical in the brain responsible for controlling body movements. This was reflected in the fact that the blueberry fed animals had much better neuromotor control.
  • Targets oxidative stress and inflammation. Aging of the brain is accelerated by conditions of oxidative stress and inflammation. Blueberry is both a potent antioxidant and has pterostilbene (a phytochemical), which also been shown to significantly reduce the release of inflammatory enzymes associated with neuroinflammation.  A pterostilbene diet significantly improved water maze function in laboratory animals. Importantly, markers of cellular stress, inflammation, and AD pathology were positively effected by pterostilbene. Findings indicate that diet-achievable doses of pterostilbene is a potent modulator of cognition and cellular stress. (See study abstract "Low dose..." below.)

  • Enabling “normal” memory functioning in mice with amyloid brain plaques. Blueberry fed mice with brain plaques performed maze maneuvering tasks as effectively as mice without plaques. Mice with plaques which did not receive blueberry supplementation fared much worse. The research group discovered that blueberry increases the levels of two enzymes (kinases) in the brain related to converting short-term to long-term memory.

Side Effects

Blueberry can act as a diuretic and can affect iron absorption. Blueberries contain small amounts of tannin. In large amounts, tannins have been associated with liver and kidney damage. Consumption of high tannin supplements can also lead to esophageal or mouth cancer.
Drug Interactions

Blueberry may interfere with the effectiveness of insulin, oral drugs for diabetes, and herbal products that affect blood sugar levels. It may also block the absorption of drugs and nutrients.

There are currently no scientific recommendations as to the amount of blueberry to consume to achieve positive health benefits. 

If using the capsule form, consider the dosage advice on the container. 

Jett's bottle says 1,000 mg a day for an adult. Assuming that's for 150 lb. adult, that's 500 mg for 75 lb. child, 250 mg for 37 lb. child, 125 mg for 19 lb. child. 

I give Jett (25 lbs) 250 mg divided up into two doses a day. I give it around nap time and bed time since lots happens to the brain during sleep.


Be sure to get $10 off your first VitaCost vitamin order.

Supporting Studies

Nutrition. 2011 Mar;27(3):338-42. Epub 2010 Dec 18.
Malin DH, Lee DR, Goyarzu P, Chang YH, Ennis LJ, Beckett E, Shukitt-Hale B, Joseph JA.

University of Houston-Clear Lake, Houston, Texas, USA.


Previously, 4 mo of a blueberry-enriched (BB) antioxidant diet prevented impaired object recognition memory in aging rats. Experiment 1 determined whether 1- and 2-mo BB diets would have a similar effect and whether the benefits would disappear promptly after terminating the diets. Experiment 2 determined whether a 1-mo BB diet could subsequently reverse existing object memory impairment in aging rats.

In experiment 1, Fischer-344 rats were maintained on an appropriate control diet or on 1 or 2 mo of the BB diet before testing object memory at 19 mo postnatally. In experiment 2, rats were tested for object recognition memory at 19 mo and again at 20 mo after 1 mo of maintenance on a 2% BB or control diet.

In experiment 1, the control group performed no better than chance, whereas the 1- and 2-mo BB diet groups performed similarly and significantly better than controls. The 2-mo BB-diet group, but not the 1-mo group, maintained its performance over a subsequent month on a standard laboratory diet. In experiment 2, the 19-mo-old rats performed near chance. At 20 mo of age, the rats subsequently maintained on the BB diet significantly increased their object memory scores, whereas the control diet group exhibited a non-significant decline. The change in object memory scores differed significantly between the two diet groups.

These results suggest that a considerable degree of age-related object memory decline can be prevented and reversed by brief maintenance on BB diets.

Casadesus G, Shukitt-Hale B, Stellwagen HM, Zhu X, Lee HG, Smith MA, Joseph JA.
Nutr Neurosci. 2004 Oct-Dec;7(5-6):309-16.
Our results show that all these parameters of hippocampal neuronal plasticity are increased in supplemented animals and aspects such as proliferation, extracellular receptor kinase activation and IGF-1 and IGF-1R levels correlate with improvements in spatial memory. Therefore, cognitive improvements afforded by polyphenolic-rich fruits such as blueberries appear, in part, to be mediated by their effects on hippocampal plasticity.
[PubMed - indexed for MEDLINE]

Williams RJ, Spencer JP.
Free Radic Biol Med. 2012 Jan 1;52(1):35-45. Epub 2011 Sep 17. Review.


There is increasing evidence that the consumption of flavonoid-rich foods can beneficially influence normal cognitive function. In addition, a growing number of flavonoids have been shown to inhibit the development of Alzheimer disease (AD)-like pathology and to reverse deficits in cognition in rodent models, suggestive of potential therapeutic utility in dementia. The actions of flavonoid-rich foods (e.g., green tea, blueberry, and cocoa) seem to be mediated by the direct interactions of absorbed flavonoids and their metabolites with a number of cellular and molecular targets. For example, their specific interactions within the ERK and PI3-kinase/Akt signaling pathways, at the level of receptors or kinases, have been shown to increase the expression of neuroprotective and neuromodulatory proteins and increase the number of, and strength of, connections between neurons. Concurrently, their effects on the vascular system may also lead to enhancements in cognitive performance through increased brain blood flow and an ability to initiate neurogenesis in the hippocampus. Additional mechanisms have been suggested for the ability of flavonoids to delay the initiation of and/or slow the progression of AD-like pathology and related neurodegenerative disorders, including a potential to inhibit neuronal apoptosis triggered by neurotoxic species (e.g., oxidative stress and neuroinflammation) or disrupt amyloid β aggregation and effects on amyloid precursor protein processing through the inhibition of β-secretase (BACE-1) and/or activation of α-secretase (ADAM10). Together, these processes act to maintain the number and quality of synaptic connections in key brain regions and thus flavonoids have the potential to prevent the progression of neurodegenerative pathologies and to promote cognitive performance.
Copyright © 2011 Elsevier Inc. All rights reserved.

[PubMed - indexed for MEDLINE]

Acosta S, Jernberg J, Sanberg CD, Sanberg PR, Small BJ, Gemma C, Bickford PC.
Rejuvenation Res. 2010 Oct;13(5):581-8. Epub 2010 Jun 29.


The process of aging is linked to oxidative stress, microglial activation, and proinflammatory factors, which are known to decrease cell proliferation and limit neuroplasticity. These factors may lead the transition from normal aging to more severe cognitive dysfunction associated with neurodegenerative diseases. We have shown that natural compounds such as polyphenols from blueberry and green tea and amino acids like carnosine are high in antioxidant and antiinflammatory activity that decreases the damaging effects of reactive oxygen species (ROS), in the blood, brain, and other tissues of the body. Furthermore, we have shown that the combination of these nutrients (called NT-020) creates a synergistic effect that promotes the proliferation of stem cells in vitro and in vivo. In the current study, we examined the effects of NT-020 on neurogenesis and performance on a Morris water maze (MWM). Aged (20-month-old) male Fischer 344 rats were treated with 135.0 mg/kg per day (n = 13) of NT-020. Young (3-month-old) (n = 10) and aged (20-month-old) (n = 13) control male Fischer 344 rats were treated with water by oral gavage. All groups were treated for a period of 4 weeks. Although there was no difference in performance in the MWM when comparing all aged rats, when the data for aged impaired rats were compared, there was a significant difference between groups on the last day of training with the treatment group performing better than controls. Using the cell cycle-regulating protein (Ki67), doublecortin (DCX), and OX6 antibody markers, cell proliferation, neurogenesis, and microglial activation were estimated in the dentate gyrus (DG) of young and aged animals. Cell proliferation was also examined in the subventricular zone (SVZ). A decreased number of OX6 MHC II-positive cells, increased neurogenesis, and increased number of proliferating cells were found in rats treated with NT-020 in comparison with aged control rats. In sum, NT-020 may promote health, proliferation, and maintenance of neurons in the age animals and exert antiinflammatory actions that promote function in the aged stem cell niche.
PMID: 20586644

PMCID: PMC3014764Free PMC Article

Effect of a wild blueberry (Vaccinium angustifolium) drink intervention on markers of oxidative stress, inflammation and endothelial function in humans with cardiovascular risk factors.

Wild blueberries may protect DNA from damage, Article.
Juice made from wild blueberries may reduce oxidative damage to DNA by around 3% and decrease the risk of cardiovascular and degenerative diseases, suggests new data.


DeFENS, Department of Food, Environmental and Nutritional Sciences, Università degli Studi di Milano, via Celoria 2, 20133, Milan, Italy,



Wild blueberries (WB) (Vaccinium angustifolium) are rich sources of polyphenols, such as flavonols, phenolic acids and anthocyanins (ACNs), reported to decrease the risk of cardiovascular and degenerative diseases. This study investigated the effect of regular consumption of a WB or a placebo (PL) drink on markers of oxidative stress, inflammation and endothelial function in subjects with risk factors for cardiovascular disease.


Eighteen male volunteers (ages 47.8 ± 9.7 years; body mass index 24.8 ± 2.6 kg/m(2)) received according to a cross-over design, a WB (25 g freeze-dried powder, providing 375 mg of ACNs) or a PL drink for 6 weeks, spaced by a 6-week wash-out. Endogenous and oxidatively induced DNA damage in blood mononuclear cells, serum interleukin levels, reactive hyperemia index, nitric oxide, soluble vascular adhesion molecule concentration and other variables were analyzed.


Wild blueberry drink intake significantly reduced the levels of endogenously oxidized DNA bases (from 12.5 ± 5.6 % to 9.6 ± 3.5 %, p ≤ 0.01) and the levels of H(2)O(2)-induced DNA damage (from 45.8 ± 7.9 % to 37.2 ± 9.1 %, p ≤ 0.01), while no effect was found after the PL drink. No significant differences were detected for markers of endothelial function and the other variables under study.


In conclusion, the consumption of the WB drink for 6 weeks significantly reduced the levels of oxidized DNA bases and increased the resistance to oxidatively induced DNA damage. Future studies should address in greater detail the role of WB in endothelial function. This study was registered at as ISRCTN47732406.
PMID: 22733001

Bachstetter AD, Jernberg J, Schlunk A, Vila JL, Hudson C, Cole MJ, Shytle RD, Tan J, Sanberg PR, Sanberg CD, Borlongan C, Kaneko Y, Tajiri N, Gemma C, Bickford PC.
PLoS One. 2010 May 5;5(5):e10496.


Adult stem cells are present in many tissues including, skin, muscle, adipose, bone marrow, and in the brain. Neuroinflammation has been shown to be a potent negative regulator of stem cell and progenitor cell proliferation in the neurogenic regions of the brain. Recently we demonstrated that decreasing a key neuroinflammatory cytokine IL-1beta in the hippocampus of aged rats reversed the age-related cognitive decline and increased neurogenesis in the age rats. We also have found that nutraceuticals have the potential to reduce neuroinflammation, and decrease oxidative stress. The objectives of this study were to determine if spirulina could protect the proliferative potential of hippocampal neural progenitor cells from an acute systemic inflammatory insult of lipopolysaccharide (LPS). To this end, young rats were fed for 30 days a control diet or a diet supplemented with 0.1% spirulina. On day 28 the rats were given a single i.p. injection of LPS (1 mg/kg). The following day the rats were injected with BrdU (50 mg/kg b.i.d. i.p.) and were sacrificed 24 hours after the first injection of BrdU. Quantification of the BrdU positive cells in the subgranular zone of the dentate gyrus demonstrated a decrease in proliferation of the stem/progenitor cells in the hippocampus as a result of the LPS insult. Furthermore, the diet supplemented with spirulina was able to negate the LPS induced decrease in stem/progenitor cell proliferation. In a second set of studies we examined the effects of spirulina either alone or in combination with a proprietary formulation (NT-020) of blueberry, green tea, vitamin D3 and carnosine on the function of bone marrow and CD34+ cells in vitro. Spirulina had small effects on its own and more than additive effects in combination with NT-020 to promote mitochondrial respiration and/or proliferation of these cells in culture. When examined on neural stem cells in culture spirulina increased proliferation at baseline and protected against the negative influence of TNFalpha to reduce neural stem cell proliferation. These results support the hypothesis that a diet enriched with spirulina and other nutraceuticals may help protect the stem/progenitor cells from insults.
PMID: 20463965
Free PMC Article

Neurobiol Aging. 2012 Sep;33(9):2062-71. Epub 2011 Oct 7.

Low-dose pterostilbene, but not resveratrol, is a potent neuromodulator in aging and Alzheimer's disease.


Department of Neuroscience, Case Western Reserve University, Cleveland, OH, USA.


Recent studies have implicated resveratrol and pterostilbene, a resveratrol derivative, in the protection against age-related diseases including Alzheimer's disease (AD). However, the mechanism for the favorable effects of resveratrol in the brain remains unclear and information about direct cross-comparisons between these analogs is rare. As such, the purpose of this study was to compare the effectiveness of diet-achievable supplementation of resveratrol to that of pterostilbene at improving functional deficits and AD pathology in the SAMP8 mouse, a model of accelerated aging that is increasingly being validated as a model of sporadic and age-related AD. Furthermore we sought to determine the mechanism of action responsible for functional improvements observed by studying cellular stress, inflammation, and pathology markers known to be altered in AD. Two months of pterostilbene diet but not resveratrol significantly improved radial arm water maze function in SAMP8 compared with control-fed animals. Neither resveratrol nor pterostilbene increased sirtuin 1 (SIRT1) expression or downstream markers of sirtuin 1 activation. Importantly, markers of cellular stress, inflammation, and AD pathology were positively modulated by pterostilbene but not resveratrol and were associated with upregulation of peroxisome proliferator-activated receptor (PPAR) alpha expression. Taken together our findings indicate that at equivalent and diet-achievable doses pterostilbene is a more potent modulator of cognition and cellular stress than resveratrol, likely driven by increased peroxisome proliferator-activated receptor alpha expression and increased lipophilicity due to substitution of hydroxy with methoxy group in pterostilbene.
Copyright © 2012 Elsevier Inc. All rights reserved.
PMID: 21982274

  1. Andres-Lacueva C, et al. Anthocyanins in aged blueberry-fed rats are found centrally and may enhance memory. Nutr Neurosci. 2005 Apr;8(2):111-20.
  2. Barros D, et al. Behavioral and genoprotective effects of Vaccinium berries intake in mice. Pharmacol Biochem Behav. 2006 Jun;84(2):229-34.
  3. Joseph, James. Nutrition and brain function food for the aging mind. USDA-Agriculture Research Services. August 2007.

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