Health Benefits of Blueberries

1. Health Benefits of Blueberries

2. Introduction • The consumption of blueberries may have some beneficial effects against chronic diseases including • Alzheimer’s Disease • Diabetes • Cardiovascular Diseases • Cancer • Health benefits are associated to its polyphenolic compounds • There are no current reports related to toxicity levels

3. Introduction • Chemical composition may vary according to season, environment, and variety • Blueberries are rich in: • Anthocyanins • Proanthocyanidins • Flavan-3-ols • Flavonols • Phenolic acids • Hidroxycinnamic acid (Atalay and others 2003, Schmidt and others 2004, 2006,)

4. Alzheimer’s Disease (AD) 4.5 million Americans have AD. Ten percent of those older than 65, and 1 of 2 people at age 85 will be diagnosed with AD Women have a greater incidence than men. Alzheimer causes: Genetics (Chromosome 21) Head Trauma Viral agents Environmental factors Organic solvents, aluminum, coffee, alcohol consumption, and medication use. (McCollom 2004)

5. Alzheimer’s Disease • AD is a dementia disease, progressive and degenerative causing the loss of intellectual functions: • Thinking • Remembering • Sequencing • Reasoning • Behavior • AD is characterized by the neurofibrillary tangles and senile plaques (amyloid β peptide) (McCollom 2004, Ramassamy 2006).

6. Amyloid βpeptide toxicity Toxicity Mechanisms Activation of the NF-κB Apoptosis Mitochondrial Dysfunction Neuronal Death (Ramassamy 2006)

7. Consequences Toxicity of the amyloid β peptide involves transition metals, formation of hydrogen peroxide, accumulation of reactive oxygen species and oxidative stress (Ramassamy 2006). The brain is especially susceptible to oxidative stress since it weighs 2% of the body mass and it utilizes 20% of the total oxygen consumed by the body. Normal brain aging is also associated with elevated levels of neuroinflammation (activation of NF-κB) which increases ROS production (Lau and others 2005).

8. Food intake benefits Epidemiological evidence indicates that phytochemicas may provide neuroprotection against age-related neurodegenerative disorders(Ramassamy 2006). Polyphenols could have therapeutical potential for these pathologies. Blueberries, have been found to be beneficial to brain function. Blueberries contain high levels of polyphenolic flavonoids(Dunlap and others 2005, Duffy and others 2007).

9. AD: Current Research • Lau and others (2005) • Aged rats supplemented with blueberries extracts showed: • Reversed age-related deficits in neuronal and cognitive function • By increasing the levels of ERK and CKC which are important in mediating cognitive functions especially in conversion to short-term to long-term memory • Increase in hippocampal, plasticity and cognitive performance in mice via concerted mechanisms involving • Neurogenesis, neurotrophic factor IGF-1 and its receptor, and MAP kinase signal transduction cascades

10. Diabetes Statistics • 20.8 million children and adults in the U.S, or 7% of the population have diabetes (ADA 2007) • 180 million people worldwide (WHO 2007)

11. Diabetes mellitus • Chronic disease • Deficiency in production of insulin by the pancreas • Ineffectiveness of the insulin produced • Increased concentrations of glucose in the blood damage many of the body's systems, in particular the blood vessels and nerves(WHO 2007)

12. Type 1 diabetes • The pancreas fails to produce the insulin which is essential for survival • Most frequently • Children and adolescents (WHO 2007)

13. Type 2 diabetes • The body's inability to respond properly to the action of insulin produced by the pancreas. • More common (90% of cases worldwide) • Adults • It is being noted increasingly in adolescents (WHO 2007)

14. Importance of food intake • Because food intake affects the body's need for insulin and insulin's ability to lower blood sugar, diet is the basis of diabetes treatment (FDA 2007) • Studies in healthysubjects and those at risk for type 2 diabetes support the importanceof including foods containing • Carbohydrate particularly from: • Whole grains • Fruits, vegetables • Low-fat milk (ADA, 2002)

15. Diabetes and oxidative stress • Diabetes may be a state of increased oxidative stress • There has been interest in prescribing antioxidant vitaminsto people with diabetes (ADA 2002) • Blueberry constituents are likely to act by mechanisms that: • Counteract oxidative stress • Decrease inflammation • Modulate molecular interactions and expression of genes associated with disease processes (Neto 2007)

16. Diabetes: Current Research • Haddad 2001performed an ethnopharmacological survey of the most used antidiabetic medicinal in Québec and Morocco • Vaccinium spp. (blueberry) received firstplace • Improves themicrovascular and lipid perturbations associated with diabetes

17. Diabetes: Current Research • Shane (2001) investigated blueberry’s leaves • Traditionally been used to control blood sugar levels in people with diabetes • Lowers blood sugar • Could make the effect of diabetes medication stronger

18. Diabetes: Current Research • Cignarella and others (1996 ) studied the effect of an hydroalcoholic extract of blueberry leaves orally administered to diabetic rats. • Plasma glucose levels were consistently found to drop by about 26%

19. Diabetes: Current Research • Eveleen (2006) tested blood glucose levels in diabetic and non diabetic subjects • 100 g of fresh berries for one month • 14.54 and 9.9 % decrease in blood sugar levels in diabetic and non diabetic subjects respectively.

20. Diabetes: Current Research • Martineau and others (2006) tested ethanol extracts of root, stem, leaf and fruit using multiple cell-based bioassays • Tested at 12.5 µg/ml • Blueberries have insuline-like activity • Exhibit anti-diabetic effects in pancreatic  cells

21. Cardiovascular Disease (CVD) • A general term for all diseases of the heart and blood vessels • Almost 1 million Americans die of CVD every year • 40.6% of all deaths • CVD is nation’s No. 1 killer CDC 2007

22. Chronic Endothelial Injury and the Progression of CVD

23. Atherosclerosis Hardening, loss of elasticity, and thickening of arterial walls with narrowing of the lumen of the artery. Principal cause of myocardial infarction and stroke (heart and brain attack).

24. CVD: Current Research • Heinonen and others (1998) reported the antioxidant activity of phenolic compounds present in berries by two coppercatalyzed in vitro oxidation assays: • LDL • LDL oxidation was inhibited by 68.4 –89.0 % at 10 M and 20 M GAE respectively • Lecithin liposomes • By 41.2 and 77.1 % measured by the formation of hydroperoxides (ROOH) and hexanal respectively at concentration 20 M GAE

25. CVD: Current Research • Prior and Cooke (2004) studied the inhibition of platelet aggregation • An inhibition of 38% of platelet aggregation was observed in individuals who consumed 1 cup of blueberries in their normal diet for 2 weeks

26. CVD: Current Research • Norton and others (2005) studied how a blueberry enriched diet protected rat arteries from contracting • Rats fed with an enriched diet generated less force in response to phenylephrine, a stress hormone, than did arteries in rats fed the same diet without blueberries

27. CVD: Current Research • Ahmet and others (2007) studied how a blueberry-enriched diet protects rat’s heart from Ischemic damage • The myocardial infarction (MI) in blueberry diet was 24% less than in control diet

28. Risk Factors You Can Change, Treat or Modify High blood pressure High blood cholesterol Tobacco smoke Overweight and obesity Physical inactivity Diabetes (AHA 2007)

29. Make Healthy Lifestyle Changes Control high blood pressure Don’t smoke. If you smoke, quit. Maintain healthy cholesterol levels Be physically active Control or delay the onset of diabetes Reduce excess weight or maintain a healthy weight Eat a healthful diet F&V.

30. CancerStatistics • Cancer is the result of a combination of one or more factors: • Genetic mutation • Environment • Lifestyle • Age • Diet

31. Cancer Statistics • According to the WHO, there are every year more than 10 millions new cancer cases in the world (Surh 2003) and this number may be double in the next 20 years (Pecorino 2006). • In 2003, 1.3 millions new cases of cancer were diagnosed in USA and from those 550, 000 died from cancer (Surh 2003).

32. Cancer Statistics • Cancer of thelung and thelargeintestin (colon and rectum) are themostsignificant in bothgenders. • Specificcancersbygender: • Women: Breast • Men: Prostate (Schulz 2005) (Cancer Research Institute 2003)

33. Cancer Statistics • Diet has been identified as responsible of influencing the cancer risk. • Researchers have estimated that about 30 - 40% of all cancer cases are related to dietary habits. (Davis and Milner 2007; Surh 2003)

34. Cancer “Group of diseases (>200) characterized by unregulated cell growth and the invasion and spread of cells from the site of origin to other site in the body.”

35. Cancer • Carcinogenesis: “Process that involves several steps in which distinct molecular and cellular alteration occurs” • Three steps: • Initiation • Promotion • Progression • (D'Ambrosio 2007; Surh 2003)

36. Cancer and Phytochemicals • Prevention of initiation process by blueberry phytochemicals may involve: • Inactivation of carcinogens • Inhibition of phase I enzymes • Induction of phase II enzymes • Blueberry phytochemicals may also inhibit promotion or progression by eliminating cancer cells or inhibiting their growth.

37. Cancer: Current Research • Kraft and others (2005) worked with blueberry extracts to study the chemoprevention effect. • Chemical composition may protect against the initiation, promotion and progression of carcinogenesis. • Chemical compounds found were phytosterols, phenolic acids, flavan-3-ols, anthocyanins, and oligomeric proanthocyanidins; that may interact synergistically, concomitantly, or additively to enhance its bioactivity.

38. Cancer: Current Studies • Schmidt and others (2004) worked with fractions rich in proanthocyanidins demonstrated a significance positive correlation between proanthocyanidins content and antiproliferation assays. • Schmidt and others (2006) studied wild and cultivated blueberry to see bioactivity against the proliferation prostate cancer cell lines. • Blueberry (wild and cultivated) fractions rich in proanthocyanidins have an effect on androgen dependant growth of cancer cell line.

39. Cancer: Current Research • Srivastava and others (2007) identified the presence of delphinidin, cyanidin, peonidin, petunidin and malvidin as the major anthocyanins in blueberry extracts. • Anthocyanins rich fraction might increase apoptosis as well as the activity of detoxifying enzymes quinone reductase and glutathione S-Trasnferesase.

40. Cancer: Current Research • Smith and others (2000), studied the bioactive activity of several fractions of blueberry extracts. • Crude extract made of 70% acetone (proanthocyanidins and anthocyanins), showed induction of quinone reductase activity, which indicates a potential for inhibiting the initiation stage of carcinogenesis.

41. Cancer: Current Research • Yi and others (2005) studied the bioactivity of phenolic compounds in several fractions obtained from rabbiteye blueberry to assess the potential as an antiproliferative and apoptosis induction on colon cancer cells. • Phenolic compounds could inhibit cancer cell proliferation and induce cell apoptosis. • From the four fractions obtained (phenolic acids, tannins, flavonols and anthocyanins), the anthocyanins fraction showed the highest antiproliferation and induction of apoptosis.