BLUEBERRY

BACKGROUND

Ingredient Type: Botanical

Also Known As: Vaccinium angustifolium, Lowbush blueberry, Common lowbush blueberry

Originally blueberries, also known as “Highbrush Blueberries,” were considered wild until during the early 20th century when the daughter of a New Jersey farmer, Elizabeth White, was determined to domesticate the wild berry. She teamed up with USDA botanist Frederick Coville to identify which wild plants with the most desirable properties could work to create new blueberry varieties. The first successful, harvested crop of blueberries was sold out of Whitesbog, New Jersey, in 1916 (1). From this time forward, blueberries have been a main staple, farm to table antioxidant-packed fruit readily consumed as a food, a medicine, and even as a source for natural flavoring.

According to the National Nutrient Database, blueberries are low in calories and high in fiber. They are abundant in the following vitamin sources: vitamin C, vitamin K, vitamin B6, folate, potassium, copper, and manganese. Blueberries are low in carbohydrates and sodium and are high in water content. They are also high in antioxidants, especially anthocyanin, along with other flavonoids (3).

TRADITIONAL USES

Blueberries have traditionally been used for cataract and glaucoma prevention along with treating ulcers, urinary tract infections (UTIs), multiple sclerosis (MS), chronic fatigue syndrome (CFS), colic, fever, varicose veins, and hemorrhoids. For thousands of years in European medicine, blueberries have been used primarily to treat diarrhea. Although not as many studies are out on the use of blueberry leaves, this part of the plant has been historically used to control blood sugar levels in those with diabetes.

WHAT DOES SCIENCE TELL US?

Blueberries Might Support a Healthy Cardiovascular System:

In a randomized-controlled study, the effects of blueberry supplementation on various features of metabolic syndrome, lipid peroxidation, and inflammation in obese men and women were assessed. Forty-eight participants with metabolic syndrome (4 males and 44 females) each consumed a freeze-dried blueberry beverage or an equivalent amount of fluids (control group – 960 mL of water) over 8 weeks. From the results, it was noted that there were significant decreases in systolic and diastolic blood pressures in the blueberry group vs. the control group. Serum glucose and lipid profiles, however, were not affected in this study. There were also noted decreases in plasma oxidized LDL and serum malondialdehyde and hydroxynonenal concentrations in the blueberry group than in the control group. It was concluded from this study that blueberries might have a cardioprotective effect on certain cardiovascular risk factors in those with metabolic syndrome (5).

A paper reviewed the effects of grapes and other berries on global cardiovascular health. Upon assessment of multiple, recent clinical, and observational studies, it suggested that the flavonoids present in berries may be particularly associated with cardiovascular benefits. According to their research, analyzed human clinical data studies support the following cardioprotective benefits of grapes and berries: inhibition of platelet aggregation, decreased low-density lipoprotein oxidation, reduction in oxidative stress and improvements in endothelial function (6).

In another study, the researchers hypothesized that daily consumption of blueberry would increase natural killer (NK) cells and plasma redox capacity while reducing blood pressure, augmentation index (AIx), central pulse wave velocity and aortic systolic pressures (ASPs). This randomized study consisted of 25 men and postmenopausal women (aged 18-50 years old) that were assigned to a BB (n = 13) or placebo (n = 12) group. In the BB group, participants consumed 250 g of berries daily for six weeks while the placebo consumed placebo powders daily for six weeks. The makers measured before the start and following the completion of the study were: blood pressure, vascular performance testing, and a serum panel. The overall Aix and ASPs were notably decreased in the BB group while the plasma redox was not affected. Additionally, the absolute NK cells were increased in the BB group as well when compared to the placebo group. It was concluded from the results that BB ingestion for 6-weeks increases NK cells while reducing Alx, ASPs, and diastolic pressures in sedentary male and female adults (16).

One interesting trial followed up on 93,600 healthy women ages 25-42 years old to examine the relationship between anthocyanins and other flavonoids and the risk of MI. Flavonoid intake was calculated from validated food-frequency questionnaires collected over a 4-year timeframe. During 18 years of follow-up, 405 cases of MI were reported. An inverse association between higher intake and risk of MI was observed based on the collected data. It was noted that a combined intake of 2 anthocyanin-rich foods, blueberries, and strawberries tended to be associated with decreased risk of MI in comparison to those consuming > 3 servings a week than those with lower intake. It was concluded that a high intake of anthocyanins might reduce MI risk in predominantly young women (17).

Blueberries Possibly Support Healthy Cell Growth:

A study investigated the chemoprotective activity of blueberry extract in triple-negative breast cancer cell lines in vitro and in vivo. The following activities were noted from this study:

– Decreased cell proliferation in HCC28, HCC 1937 and MDA-MD-231 cell lines with no effect on the non-tumorigenic MCF-10A cell line

– Decreased activity of matrix metalloproteinase-9 and the secretion of urokinase-type plasminogen activator while increasing tissue inhibitor of metalloproteinase-1 and plasminogen activator inhibitor-1 secretion in MDA-MB-231 conditioned medium

– Decreased metastatic potential of MDA-MB-231 cells through cell motility inhibition

– Decreased phosphatidylinositol 3-kinase and NFkB activation in MDA-MB-231 cells

– Tumor weight and proliferation were decreased in blueberry treated mice, where apoptosis was increased compared with controls

This study illustrated the inhibitory effect of blueberry phytochemicals on the growth and metastatic potential of MDA-MB-231 cell lines (8).

Another study was designed and conducted to assess the effectiveness of blueberry dietary supplementation on diethylnitrosamine-initiated (DEN) hepatocarcinogenesis in male Wistar rats. Three groups were utilized in this study. The first group served as the control group; the second group received DEN (10 mg/kg) 5Xs/week while the third group received DEN with a 4% blueberry supplemented diet. The following results were noted from this study: a significant decrease in elevated serum levels of a-fetoprotein, homocysteine along with levels of glutathione, deoxyribonucleic acid, ribonucleic acid and activity of glutathione reductase in the liver. Additionally, there were significantly noted increases in reduced hepatic activity of xanthine oxidase, while histopathological damage was minimized in the blueberry supplement group. From this study, it was concluded blackberry suppresses the DEN-induced hepatocarcinogenesis and could be further used as a potential chemo-preventive natural supplement for liver cancer (9).

A study was designed to examine the effects of 3 flavonoid-enriched fractions (crude, anthocyanin-enriched, proanthocyanidins-enriched fraction), which were prepared from lowbush blueberries on MMP activity in DU145 human prostate cancer cells in vitro. The MPP activity was evaluated from the cells over a 24-hour exposure to the respective blueberry fractions. From the results, it was noted that all three flavonoid-enriched fractions exhibited an ability to decrease the activity of MMP-2 and MMP-9. The proanthocyanidin-enriched fraction was noted to exhibit the most inhibition of MPP activity in the DU145 human prostate cancer cells. It was also noted that there was no indication of either necrotic or apoptotic cell death associated with the application of the blueberry fractions. It was concluded from the observed data that flavonoids from blueberry possess the ability to effectively decrease MMP activity, which may be an important factor in controlling tumorigenesis and metastasis of DU145 human prostate cancer cells (11).

Blueberries Possibly Support Healthy Blood Sugar:

Blueberries in pre-clinical studies resulted in a gradual decrease in glucose concentrations. This double-blind, randomized, placebo-controlled study sought to evaluate the effect of daily consumption of blueberries on whole-body insulin sensitivity in obese men and women. Thirty-two obese participants who were non-diabetic and insulin-resistant had baseline as well as concluding measurements of serum inflammatory biomarkers and adiposity. The participants were randomly assigned to either consume a smoothie containing 22.5 g blueberry bioactives or a smoothie of equal nutritional value without added blueberry bioactives 2x’s daily for 6-weeks. Participant weights were assessed weekly along with food records being collected at baseline, in the middle, as well as at the conclusion of the study. The results noted that the mean changes in insulin sensitivity improved more in the bioactive blueberry group than the placebo group. Insulin sensitivity was improved in the bioactive blueberry group, although there were no noted significant changes in adiposity, energy intake, or other inflammatory biomarkers. From this study, it was concluded that supplementation with bioactives from whole blueberries improves insulin sensitivity in obese, non-diabetic, insulin-resistant individuals (7).

Blueberries Possibly Support Cognition:

In a cross-over study, the aim was to investigate whether there are associated cognitive benefits to supplementation of blueberry infused flavonoid beverages on 8 to 10-year-olds. 14-children ages 8 to 10 consumed either a flavonoid-rich blueberry drink or a matched beverage in caloric and nutrient content. 2-hours post-consumption, the children completed a battery of five cognitive tests comprising of Go-NoGo, Stroop, Rey’s Auditory Verbal Learning Task, Object Location Task, and Visual N-Back. From the analyzed results, it was noted that the blueberry group produced significant improvements in delayed recall of previously learned lists of words, showing for the first time a cognitive benefit for acute flavonoid intervention in children. There, however, was no observed benefit of blueberry intervention for measures of attention, response inhibition, or visuospatial memory from this stud. Other observations noted during the trial: delayed memory recall improved in the blueberry group vs. the control group, proactive interference increased in the blueberry group vs. the control group, no effect was noted in the executive function of tasks. Although there were mixed results from this study, it was noted that following acute flavonoid-rich blueberry interventions, school-aged children encode memory items more effectively (10).

In this study, beginning in 1980, a semiquantitative food frequency questionnaire was administered were 16,010 participants aged > 70 years were assessed for certain cognitive function markers. Using a multivariate-adjusted, mixed linear regression, the mean differences in slopes of cognitive decline were estimated between long-term berry and flavonoid intakes. From the assessed results, it was concluded that greater intake of blueberries and strawberries were associated with slower rates of cognitive decline; more specifically, greater intakes of anthocyanidins and total flavonoids were associated with the noted slower rates of cognitive decline (18).

Blueberries Might have Antioxidant Properties:

A human intervention study was designed to assess the antioxidative and potentially anti-genotoxic effects of fruit-borne antioxidants. It was hypothesized that individuals bearing genetic polymorphisms for genes related to quercetin metabolism, benzo(a)pyrene metabolism, oxidative stress, and DNA repair differ in their response to DNA protective effects of increased antioxidant intake. In this study, 168 healthy volunteers consumed a blueberry/apple juice providing 97 mg quercetin and 16 mg ascorbic acid per day. Following a 4-week interventional period, plasma concentrations of quercetin and ascorbic acid and Trolox equivalent antioxidant capacity (TEAC) were significantly increased. From the assessment of the 34 biologically relevant genetic polymorphisms, six significantly influenced the outcome of the intervention. Lymphocytes from individuals bearing a variant genotype for Cyp1B1 seemed to benefit more than wild-types from DNA damage-protecting effects upon intervention. Variants for COMT tended to benefit less or even experienced detrimental effects from the intervention. From this data, it was concluded that genotyping for relevant polymorphisms enables selecting subgroups among the general population to recognize if more benefit will come from certain DNA damage-modulating effects of specific micronutrients (13).

Another study was conducted to investigate the effects of regular consumption of a wild-berry (WB), or a placebo (PL) drink on markers of oxidative stress, inflammation, and endothelial function in subjects with presently elevated cardiovascular disease risk factors. In the study, 18 male volunteers received either a WB (25 g freeze-dried powder, providing 375 mg of anthocyanins or a PL drink for a duration of 6 weeks, which was spaced out by a 6-week washout period. The results noted that the group who consumed the WB drink had significantly reduced levels of endogenously oxidized DNA bases along with decreased levels of H2O2-induced DNA damage vs. no effect from the group consuming the PL drink. From this study, it was gathered that consumption of a WB drink for six weeks significantly reduced the levels of oxidized DNA bases as well as an increase in the resistance to oxidatively induced DNA damage (14).

A cross-over designed study was conducted to determine whether consumption of blueberries could reduce postprandial oxidation when consumed during a typical high-carbohydrate, low-fat breakfast. There were 14 individuals who participated, each receiving three treatments for 3-weeks. The treatments consisted of a high blueberry dose (75 g), a low blueberry dose (35 g), and a control (ascorbic acid and sugar – matching that of what was found in the blueberry drink). The following markers were measured at fasting as well as 1, 2, and 3h following consumption of the beverages: serum oxygen radical absorbance capacity (ORAC), serum lipoprotein oxidation (LO), and serum ascorbate, urate, and glucose. According to the results, the mean serum ORAC was significantly higher in the high blueberry dose. The serum ascorbate, urate, and glucose were not, however, significantly different amongst the three groups. It was concluded that a consumable quantity of 75 g of blueberries could provide a statistically significant amount of oxidative protection in vivo following the consumption of a high-carbohydrate, low-fat breakfast (15).

SAFETY

Consumption of the blueberry fruit is considered safe for those not allergic to the plant or its budding fruit. There, however, is not enough reliable information about the safety of oral consumption of blueberry leaves, and therefore it is advised to avoid ingesting the leaves. Avoid consumption of blueberries if you think you are potentially allergic to them until ruled out by your healthcare provider.

Interactions:

Blueberry consumption may decrease blood sugar, and therefore those on diabetic medications (glimepiride, glyburide, insulin, pioglitazone, rosiglitazone, chlorpropamide, glipizide, tolbutamide) should proceed with caution when consuming blueberries as part of their diet. It is recommended to consult your healthcare provider so they can closely monitor your blood sugar for any fluctuations that can be addressed by rebalancing your medications if necessary.

Blueberries are also known in larger quantities to affect blood viscosity. Those taking blood-thinning medications (warfarin) or suffering from blood disorders (hemophilia) are recommended to avoid consuming blueberries. The vitamin K content may potentially interfere with blood-thinning and result in blood-clotting (3).

One reported incident was noted in 2016, where a female noted the following symptoms when taking blueberries with aspirin: diarrhea, flatulence, and muscle spasms (2). No other reported incidents have been recorded at this time.

Side-Effects:

As there are no real side-effects with the consumption of blueberries aside from potentially discolored stool, caution should, however, be taken in certain circumstances. For those individuals who have diabetes, it is advised to proceed with caution as blueberry consumption may lower blood sugar levels. The dose of diabetic medications may need to be adjusted from typical levels. Altered blood sugar levels may also be important when individuals are about to undergo surgery. It is recommended to stop consuming blueberries at least 2-weeks before scheduled surgery to reduce the likelihood of blood sugar imbalances before or during surgery. Lastly are those allergic or potentially allergic to the blueberry plant and its respective fruits. The most common side-effects to those who are allergic to blueberries are:

– Itching/swelling of the oral cavity, tongue or lips

– Eczema, gives, swelling and erythema of extremities or face

– Abdominal pain, nausea, vomiting or diarrhea

– Runny/stuffy nose, coughing, sneezing wheezing or anaphylaxis

– Decreased blood pressure, lightheadedness or fainting

REFERENCES

1. History of Blueberries. U.S. Highbush Blueberry Council. https://www.blueberrycouncil.org/about-blueberries/history-of-blueberries/. Accessed 1 January 2020.
2. Aspirin and Blueberries. eHealthMe. https://www.ehealthme.com/drug-interaction/aspirin/blueberries/. Accessed 1 January 2020.
3. Nagdeve M. 20 Evidence-Based Health Benefits of Blueberries. Organic Facts. https://www.organicfacts.net/health-benefits/fruit/health-benefits-of-blueberries.html. Accessed 1 January 2020.
4. Neto CC. Cranberry and Blueberry: Evidence for Protective Effects Against Cancer and Vascular Diseases. Molecular Nutrition & Food Research. 2007;51(6): 652-664.
5. Basu A, Du M, Leyva MJ, et al. Blueberries Decrease Cardiovascular Risk Factors in Obese Men and Women with Metabolic Syndrome. J Nut. 2010;140(9): 1582-1587.
6. Wightman JD, Heuberger RA. Effect of Grape and Other Berries on Cardiovascular Health.  Sci Food Agri. 2014;95(8): 1584-1597.
7. Stull AJ, Cash KC, Johnson WD, Champagne CM, Cefalu WT. Bioactives in Blueberries Improve Insulin Sensitivity in Obese, Insulin-Resistant Men and Women. J Nutr. 2010;140(10): 1764-1768.
8. Adams LS, Phung S, Yee N, Seeram NP, Li L, Chen S. Blueberry Phytochemicals Inhibit Growth and Metastatic Potential of MDA-MB-231 Breast Cancer Cells through Modulation of the Phosphatidylinositol 3-Kinase Pathway. Prevention and Epidemiology. 2010;70(9): 3594-3605. doi: 10.1158/0008-5472.CAN-09-3565
9. Sadik NAH, El-Maraghy SA, Ismail MF. Diethylnitrosamine-Induced Hepatocarcinogenesis in Rats: Possible Chemoprevention by Blueberries. African J Biochem Resear. 2008;2(3): 081-087.
10. Whyte AR, Williams CM. Effects of a Single Dose of a Flavonoid-Rich Blueberry Drink on Memory in 8 – 10-Year-Old Children. Nutrition. 2015;31(3): 531-534.
11. Matchett MD, MacKinnon SL, Sweeney M, Gottschall-Pass KT, Hurta RAR. Blueberry Flavonoids Inhibit Matrix Metalloproteinase Activity in DU145 Human Prostate Cancer Cells. Biochemistry & Cell Biology. 2005;83(5): 637-643.
12. Riso P, Klimis-Zacas D, et al. Effect of Wild Blueberry (Vaccinium angustifolium) Drink Intervention on Markers of Oxidative Stress, Inflammation and Endothelial Function in Humans with Cardiovascular Risk Factors. Eur J Nutr. 2013;52(3): 949-961.
13. Wilms LC, Boots AW, de Boer VC, Maas LM, et al. Impact of Multiple Genetic Polymorphisms on Effects of a 4-Week Blueberry Juice Intervention on ex vivo Induced Lymphocytic DNA Damage in Human Volunteers. Carcinogenesis. 2007;28(8): 1800-1806.
14. Riso P, Klimis-Zacas D, Del Bo C, Martini D, et al. Effect of a Wild Blueberry (Vaccinium angustifolium) Drink Intervention of Markers of Oxidative Stress, Inflammation and Endothelial Function in Humans with Cardiovascular Risk Factors. Eur J Nutr. 2013;52(3): 949-961
15. Blacker BC, Snyder SM, Eggett DL, Parker TL. Consumption of Blueberries with a High Carbohydrate, Low-Fat Breakfast Decreases Postprandial Serum Markers of Oxidation. Br J Nutr. 2013;109(9): 1670-1677.
16. McAnulty LS, Collier SR, Landram MJ, Whittaker DS, et al. Six Weeks Daily Ingestion of Whole Blueberry Powder Increases Natural Killer Cell Counts and Reduces Arterial Stiffness in Sedentary Males and Females. Nutr Res. 2014;34(7): 577-584.
17. Cassidy A, Mukamal KJ, Liu L, Franz M, Eliassen AH, Rimm EB. High Anthocyanin Intake is Associated with a Reduced Risk of Myocardial Infarction in Young and Middle-Aged Women. Circulation. 2013;127(2): 188-196.
18. Devore EE, Kang JH, Breteler MM, Grodstein F. Dietary Intakes of Berries and Flavonoids in Relation to Cognitive Decline. Annals of Neurology. 2012;72(1): 135-143.

PRODUCTS THAT CONTAIN THIS INGREDIENT

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