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A healthy blend of polyphenols from Canadian wild blueberries and french grapes

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CerebelleTM: promoter of your brain healthWhat is CerebelleTM?CerebelleTM is a standardized mixture of extracts obtained from Canadian wild blueberries and French grapes. Blueberries are a major source of proanthocyanidins (PACs) and phenolic acids (chlorogenic acid), while grapes are a rich sources of stilbenes and flavonols (catechins and epicatechins). Traditionally, products known to contain these molecules have been associated with the protection of cognitive functions. The proprietary process developed for the extraction of these molecules allows reaching concentrations of flavonols up to 29% (29% TF). The antioxidant capacity of CerebelleTM has been measured at 21,000 in ORAC (μmols Trolox/g of dry weight). CerebelleTM comes in powder form and is low in calories.

CerebelleTM Content(% of total polyphenols)

0 10 20 30 40 50

Flavonols/phenolic acids

Resveratrol

Anthocyanins

Proanthocyanidins

Epicatechins

Catechins

CerebelleTM: what for?CerebelleTM is indicated in the prevention of the normal cognitive decline associated with aging (primary cognitive decline). The national institute on Aging (a division of the NIH) estimates that by 2050, the number of people aged of 65+ will represent more than 16% of all individuals worldwide, for a total just under 1.5 billion. Data from recent studies have shown that the prevalence of mild cognitive impairment in the population of 70 to 75 years of age to be between 15 to 20%. Changes in life style (including increase consumption of polyphenols from fruits and vegetables) have now been associated, along with exercising and good control of high blood pressure, with a lower risk of developing dementia in elderlies. CerebelleTM is providing in a daily dose the equivalent of polyphenols contained in 150 grams of fresh fruit.

CerebelleTM: bioavailability and excretion.The bioavailability of the different components in CerebelleTM has been studied both in animal and human with consistent results showing that the combination of wild blueberry and grape extract is increasing the bioavailability of chlorogenic acid (a compound unique to wild blueberry) which has been demonstrated in the in vitro human cell line study to prevent oxidation of neuronal cells.

The human CerebelleTM

clinical study was also successful to demonstrate a significant higher excretion rate of epicatechins, catechins and their metabolites, and a lower secretion of chlorogenic acid, confirming the positive interaction of both extract in changing absorption profile of phenolic compounds.

Polyphenols that fight aging

Recent research suggests that dietary supplementation with wild blueberry extract is effective in reversing age-related brain deficits and behaviorial function (Shukitt-Hale. 2008). Furthermore, epidemiologic evidence has implicated that dietary polyphenols from grape may protect against cognitive deterioration in aging. (Pasinetti, 2012). In the brain, aging is generally associated with cumulative oxidative and inflammatory insults, as defense mechanisms weaken. A key to reduce the incidence of age-related cognitive deficits might thus be to act on the neuronal environment to prevent or dim neuroinflammation and oxidative stress-induced neurotoxicity (Vauzour, 2010). CerebelleTM has just the right polyphenol profile to support such neuroprotective, antioxidant, and anti-inflammatory activities.

PLASMA CONCENTRATION

Metabolite Control Blueberry Grape CerebelleTM

Gallic acid ND 189,2 ± 31,8 5914 ± 1372,0 10835,0 ± 2464,0

Chlorogenic acid ND 362,0 ± 87,2 ND 1962,1 ± 783,9

Resveratrol ND ND 44,6 ± 17,3 119,7 ± 45,3

Catechin ND ND 967,7 ± 356,9 821,3 ± 227,1

Epicatechin ND ND 2704,7 ± 549,9 3700,7 ± 1058,5

Université Laval, 2015

Aging

Neuronal Dysfunction

Neuroinflammation Neurotoxicity

POLYPHENOLS POLYPHENOLS

POLYPHENOLS

Cognitiveimpairment

Alzheimer’s disease

Parkinson’sdisease

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V1

Placebo CerebelleTM

PACs Dimers B

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Epicatechin

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Catechin

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CerebelleTM has also demonstrated that it can help verbal memory and new learning (encoding new information and subsequently retrieving such verbal information) in individuals who have the low VRM score at the entry of the trial, supporting the benefit of regular supplementation of CerebelleTM to improve short memory and abilities to retrieve such information.

CerebelleTM: human clinical trialSTUDY DESIGN:CerebelleTM has been evaluated in a placebo-controlled, randomized, double-blind study, in collaboration with the Institute of Nutraceuticals and Functional Foods (INAF) at Laval University (Canada) and the National Institute for Agricultural Research (INRA) at the University of Bordeaux in France. The study investigated the effect of CerebelleTM (2 x serving of 300 mg CerebelleTM/day = 600 mg of CerebelleTM or 175 mg of flavonols) on cognitive functions in a panel of 200 healthy adults, aged 60-70, over a period of 6 months. Logical, visual, and spatial memory performances were evaluated, as well as psychological aspects such as depression, fatigue, and quality of life, often altered with cognitive decline. Blood and urine samples were collected at the beginning and at the end of the study for biochemical analysis.

CerebelleTM has demonstrated that it can helps visual memory and associated learning has assessed by the PAL test

1, Active

1, Placebo

2, Active

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4, Active

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PAL tot errors adj V1

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Placebo

-4.0

-3.5

-2.5

-0.5

-2.0

0.0

-1.5

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-3.0

-1.0

Mo

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PAL

tot

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dj V

2-V

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p=0.0151

p=0.0412

(Paired Associated Learning test) in individual who has recorded at the entry of the study the worst score at the PAL test . Therefore, regular supplementation of CerebelleTM should be largely beneficial to individuals already showing mild first signs of primary cognitive decline as measured by PAL test.

Plac

ebo

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VRM Free recall Total correct Immediate recall

-2.0

-1.5

-0.5

0.0

-1.0

p=0.0286

CerebelleTM treatment improved the performances of volunteers with the low results prior the supplementation (quartile 4)

CerebelleTM treatment improved the performances of volunteers with bad results prior the supplementation (quartiles 3 & 4)

Separation of population by quartiles following their performances at the test prior the supplementation (V1): 1 (best results) / 4 (worst results)

1 2 3 4

1 2 3 4

How does CerebelleTM works: The positive effect of CerebelleTM supplementation on cognitive functions can be explained by a modulation in the expression of genes involved in neuronal plasticity. Indeed, the brain of mice on a CerebelleTM enriched diet revealed increased of mRNA levels of nerve growth factor (NGF) and Ca2+/calmodulin-dependent protein kinase (CamKII). NGF is expressed by neurons in the hippocampus and facilitates spatial memory through an action of cholinergic neurons (Conner, 2009). CamKII is also expressed in the hippocampus. This protein kinase in involved in many signalling cascades related to learning and memory.

Expression of NGF was not influenced by age. However. CerebelleTM supplementation stimulated its production in both young and aged mice. CamKII expression was decreased in the brain of aged mice, an affect that could be reversed under CerebelleTM diet. Such results suggest that CerebelleTM supplementation may prevent or retard age-related cognitive decline, in a natural nutritional way.

Modulation of gene expressionSource: Bensalem et al, 2014

Young YoungAged Aged

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Polyphenol

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Who may benefit from CerebelleTM supplementation? The aging population in general, whether healthy or with a genetic predisposition to develop accelerated neurodegeneration, may benefit from regular supplementation with CerebelleTM. Younger adults who wish to preserve their cognitive functions may also profit from the regular consumption of CerebelleTM in conjunction with a healthy life style and activities stimulating brain (like reading or memory games).

Recommended dosage: Suggested dosage: 1 or 2 capsules of 300 mg of CerebelleTM per day at breakfast time / Duration: as long as neededStability data: Stability studies on the ingredient CerebelleTM were perfomed by two independent laboratories. Results showed that the ingredient remained stable over time.

TOTAL PHENOLS/CAPSULE, AS GALLIC ACID (FOLIN-CIOCALTEU) (UV)

Time Point Result Theoretical level

Baseline 263 mg 200

6 months 259 200

12 months 248 200

Université Laval, Canada, 2015

STABILITY DATA FOR THE CEREBELLE INGREDIENT

T0 T6

Total polyphenols 63 59

Catéchine (LC-MS) 13,7 12,3

Épicatéchine (LC-MS) 9,8 8,6

OPC (FLUO) 33 31

Anthocyanes 0,17 0,10

Resvératrol 454 439

Polyphenols Biotech, France, 2015

Chlorogenic acid

Petunidin 3 - glucoside

Quercetin glucuronide

Malvidin 3 - glucoside

0.0

0.0

0.0

0.0

3.5

15

50

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+442%

+447%

+203%

+369%

B

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B

B

G

G

G

G

N

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N

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In animal and clinical studies, it has been shown that when combined together, the extracts from wild blueberry and grape will increase the bioavailability of some key metabolites which are contributing to decrease systemic inflammation including inflammation at the brain cell levels.

It is believed that catechins from grape extract are inhibiting or saturating the efflux transporters of the enterocytes on the side of the lumen of the GI tract letting the anthocyanes from wild blueberry and grape to enter more easily the blood stream. The blood concentration as measured by UPLC-MS/MS of four metabolites specific to wild blueberry were significantly more absorbed when combined with the grape extract. It is noteworthy to observe an increase of the excretion in the stool of the individuals on the CerebelleTM group of catechins, epicatechins and their related metabolites.

Bloo

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Inhibition or saturation of efflux transporters

Blueberry extract CerebelleTM

Apical intaketransporters (SGLT, GLUT)

Basolateral transporters (M RP1, 3, 5)

Apical effluxtransporters (PgP, MRP2,

BCRP)

Anthocyanins, flavors, phenolic acids from blueberry extract

Catechins from grape extract

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Sales European office: 7, Allée Ermengarde d’Anjou • ZAC Atalante Champeaux • CS 41137 • 35011 Rennes CEDEX FRANCE

Phone : + 33 (0)2 99 29 20 30 • Fax : + 33 (0)2 99 29 21 18

This brochure concerns industry professionals. It only pertains to food ingredients not final food products. It is the responsibility of each manufacturer to verify the compliance of the final product’s labeling and communication indicated on the finished foods to be delivered as such to the consumer with respect to the current local legislation. In Europe, this is based on regulation (EC) No 1924/2006 on nutrition and health claims.

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