Blueberries are enjoyed all around the world for its sweet taste and nutritional benefits. But they actually have many potential health benefits such as cancer prevention, reduction of risk for heart complications, and even slowing the aging process. With very minimal adverse side effects, blueberries are a super-fruit that can potentially improve overall health while tasting great.

Introduction

Blueberries are popular wild fruits native to North America and nowadays commercially cultivated in at least 27 countries [R, R].

Main Beneficial Compounds in Blueberries

Blueberries contain compounds that are beneficial to human health, which include phenolic acids and various types of flavonoids [R, R, R].

Source: [R]

Flavonoids are found naturally in varying concentrations in soybeans, grains, fruits, vegetables, tea, coffee, and cocoa [R, R].

Anthocyanins are a type of flavonoid and have antioxidant, anticancer, and obesity prevention properties [R].

However, anthocyanins are very unstable under normal physical conditions and as a result, are not easily absorbed by the body. Only a small percent (0.5%-1%) of anthocyanins from food reach the bloodstream [R, R].

Most health benefits of blueberries are produced by anthocyanins directly in the gut or by traveling to the liver where they are broken down into metabolites (methylated, sulfated, or glucuronidated conjugates) or just reach the bloodstream unchanged [R].

Depending on growing conditions and maturity of the fruit, blueberries’ polyphenol content can range from 48 mg up to 304 mg/100 g of fresh fruit weight [R, R, R].

Other phytochemicals contained in blueberries include flavopiridol, ellagic acid, anethole, and resveratrol. These chemicals have been shown to have cancer preventive effects [R, R].

Blueberries are also a good source of vitamin C. 100g of blueberries contain 10 mg of vitamin C which is about 1/3 of the daily recommended intake [R, R].

Mechanism of Action

Anthocyanins have multiple beneficial and protective effects on the body, being one of the most important for the prevention of oxidation or damage to biological structures like fats, proteins, and nucleic acids. These effects are attributed to their chemical structure [R].

Anthocyanins produce a wide range of colors in plant tissues. Anthocyanins neutralize the potentially harmful effects of free radicals in the body [R].

Anthocyanins can be directly incorporated into (endothelial) cells, protecting them from oxidative damage [R, R].

Although anthocyanins can directly inhibit oxidative stress, anthocyanins can also detoxify heavy metals (chelation) and exert their effects through direct protein binding. Lab tests have demonstrated that anthocyanins stimulate detoxifying enzymes and antioxidation in cultured cells [R, R].

Health Benefits

1) Blueberries Can Help Improve Brain Function

Anthocyanins in blueberries have been associated with memory and thinking improvement as well as the mitigation of neurodegeneration [R].

Anthocyanins:

  • can cross the blood-brain barrier and travel to specific areas of the brain (hippocampus) that are associated with learning and memory [R].
  • inhibit several enzymes in the brain (JNKs, ASK1, and p38 pathways), which decreases inflammation and promotes neuronal health [R].
  • enhance brain function by stimulating the growth and development of neurons (through changes in synaptic plasticity and neurogenesis) [R, R].

In animal studies, blueberries reduced oxidative stress and improved learning. Blueberries also helped improve memory (through increasing hippocampal plasticity) [R, R, R].

In a randomized, blind controlled study involving elderly people with early memory decline, blueberry supplementation improved memory in 12 weeks. Although the sample size was relatively small, the results from blueberry consumption seem promising [R].

Blueberry consumption has also demonstrated improvements in brain functions in children. In a double-blind controlled study in children aged 7-10, blueberries improved problem-solving and memory tasks proportional to the quantity consumed. Higher blueberry consumption leads to better testing scores [R].

2) Blueberries Can Decrease the Risk for Heart Disease

Blueberry polyphenols have antioxidant properties, which may protect against heart disease [R].

Oxidative stress in heart cells not only causes inflammation but also increases its size (myocardial hypertrophy), which leads to cell death and heart disease [R].

Blueberries can also reduce high blood pressure and cholesterol [R].

3) Blueberries Can Potentially Lower Blood Pressure

Blueberries increase nitric oxide, which increases blood flow and reduces blood pressure [R, R].

Oxidative stress in the kidneys and blood vessels also contributes to increased blood pressure. Blueberries are rich in anthocyanins and vitamin C, which reduce oxidative stress and lower blood pressure [R].

In a randomized control study on young cigarette smokers, blueberry consumption helped counteract the increased blood pressure caused by smoking [R].

However, in a study (DB-RCT) of patients with metabolic syndrome, daily consumption of blueberries for 6 weeks did not improve overall blood pressure [R].

4) Blueberries Can Help Manage Diabetes

Consumption of blueberries may lower the risk of developing type 2 diabetes [R].

Flavonoids in blueberries (flavonols, flavones, flavanones, flavan-3-ols, and anthocyanins) increase insulin sensitivity in the pancreas, liver, and muscles decreasing glucose concentration and the risk of type 2 diabetes [R].

Anthocyanins stimulate the secretion of GLP-1 in the gut upon food ingestion, which then acts on the pancreas to secrete insulin [R].

In cell-based studies, blueberry extracts have demonstrated both insulin-like properties and protection from glucose toxicity. These extracts also enhance the growth and regeneration of beta cells in the pancreas, which are responsible for the secretion of insulin [R].

In a study (DB-RCT), blueberry intake significantly improved insulin sensitivity without any changes in body weight, fat percentage, or energy intake compared to the control group [R].

5) Blueberries Can Help Maintain Healthy Bones

The following essential nutrients present in blueberries are important for maintaining bone health [R, R, R].:

Oxidative stress and decreased estrogen caused by aging can decrease bone strength [R, R].

Blueberries (resveratrol) can activate the Sirt1 gene (anti-aging in cells), preventing bone loss due to aging [R].

In animal studies, polyphenols and phenolic acid byproducts of blueberries promoted bone formation properties without affecting normal bone growth [R, R].

6) Blueberries May Prevent Different Forms of Cancer

Blueberries may prevent cancer due to effects like anti-inflammation, antioxidation, inhibition of cancer growth, and increased cell death (apoptosis) in cancer cells [R].

Gallic acid from blueberries can stop the spread of cancer cells from the main tumor to other parts of the body (tumor metastasis) by stopping transmission and inducing cell death [R].

Blueberries are rich in other compounds (flavopiridol, ellagic acid, anethole, and resveratrol) that have cancer preventing properties. These compounds inhibit cancer communication (NF-κB signaling), preventing normal cells from becoming cancerous [R].

Anthocyanins in blueberries inhibit this abnormal cancer growth and increase cell death [R].

Anthocyanins are also able to inhibit cellular protein synthesis and alter DNA in cancer cells [R].

In colon cancer, blueberries slowed tumor progression in male but not in female rats [R].

7) Blueberries Can Potentially Increase Lifespan

Blueberries contain polyphenols and resveratrol, which can help increase longevity and decrease the adverse effects associated with aging [R].

Blueberries are also rich in proanthocyanidins (polyphenols), which have heart protective effects and extend life span [R, R, R].

The polyphenols from blueberries reduce oxidative stress caused by reactive oxygen species and prolong the aging process [R, R].

Blueberries have been shown to activate genes involved in anti-aging and decreasing brain function decline [R]:

  • SOD produces an enzyme (superoxide dismutase) that has anti-oxidation effects and breaks down cell-damaging molecules called superoxide radicals.
  • CAT produces an enzyme (catalase) that protects the body against oxidative stress by breaking down hydrogen peroxide.

In multiple animal studies have shown that blueberries extend the average lifespan [R, R, R, R].

However, an animal study found that blueberries extracts did not significantly increase the lifespan of healthy male mice [R].

8) Topical Blueberry Extract Can Reduce Wrinkles

The natural aging process forms skin wrinkles due to an excessive amount of reactive oxygen species [R, R].

These reactive oxygen species produce an accumulation of advanced glycation end products that slow down the growth of skin cells while increasing cell death [R, R, R].

Blueberries contain flavonoids that can inhibit advanced glycation end products through anti-oxidation [R, R].

In a randomized control study with 20 type 2 diabetic women aged 55+ years, blueberry extract and C-xyloside application to the skin for 12 weeks resulted in significant improvement in skin firmness, wrinkles, and hydration [R].

9) Blueberries Can Contribute to Weight Loss

Fruits such as blueberries with a high fiber content increase satiety and decrease fat storage [R].

Also, blueberries are rich in anthocyanins, which have beneficial effects on obesity and related metabolic complications [R].

Anthocyanins also alleviate insulin resistance, reduce obesity, and decrease cholesterol by suppressing fat production/storage in the body (through PPAR-γ and ACC genes) [R].

In a study on animals on a high-fat diet, blueberry and mulberry juice mitigated fat build up, inhibited weight gain, and decreased cholesterol [R, R, R, R].

10) Blueberry Husks With Probiotics Help Alleviate Inflammatory Bowel Disease

Blueberry husks supplemented with probiotics (B. infantis, L. gasseri, and L. plantarum) have anti-inflammatory effects in the gut [R].

Blueberry husks contain polyphenols, which have antimicrobial effects on harmful bacteria (Enterobacteriaceae) that are linked to inflammatory bowel disease [R, R, R].

Blueberry polyphenols suppress the inflammatory responses from the bacteria in the gut (microbiota), decreasing inflammatory cytokines and macrophage activity [R].

These anti-inflammatory effects can alleviate symptoms such as bleeding and pain caused by ulcerative colitis [R].

Supplementation with probiotics suppresses the growth of harmful bacteria and restores the healthy composition and function of the gut [R].

In animal studies, the combination of both blueberry husks and probiotics significantly reduced intestinal inflammation more than probiotics or blueberry husks alone [R].

11) Blueberries Can Potentially Prevent Urinary Tract Infections

Blueberries are often recommended and used to prevent urinary infections (UTI) [R].

In petri-dish studies, wild blueberry extracts inhibited the growth of the main bacteria responsible for UTI (E. Coli) [R].

Blueberries and cranberries share many basic chemical components including anthocyanidins and proanthocyanidins, and several studies (RCT) have shown that cranberries are effective at preventing symptomatic UTI in women [R, R].

12) Blueberries Can Help Detoxify Heavy Metals

Heavy metals such as arsenic, cadmium, lead, and mercury produce oxidative stress and affect essential functions, and a buildup of these metals can lead to toxicity [R].

Blueberry anthocyanins can detoxify and chelate aluminum, iron, copper, and other metals [R, R, R].

In animal studies involving cadmium-induced liver toxicity, mice treated with blueberry extracts exhibited less buildup of cadmium in the liver. Blueberry anthocyanins were able to detoxify the heavy metals back to normal levels [R].

Side Effects and Contraindications of Blueberries

While blueberries are very safe, they have constituents that can potentially cause adverse effects. These constituents include:

  • Tannins (hydrolysable and condensed) [R], which can inhibit digestion and cause digestive and gut issues [R].
  • Oxalates [R, R], which can bind to calcium forming kidney stones (calcium oxalate) [R].
  • Benzoates [R], which have been linked to chronic hives (urticaria), asthma, atopic dermatitis, rhinitis, and anaphylaxis [R].

Despite the safety and positive health effects of blueberry consumption, over consumption may have some potential adverse effects.

  • Blueberries can decrease blood sugar: Blueberries are rich in anthocyanins which have glucose lowering effects in the body. This can be dangerous for medicated diabetic patients with low blood sugar [R].
  • Over-consumption of blueberries can prevent blood clotting, causing excessive bleeding from cuts and lacerations. Resveratrol can decrease blood clotting by inhibiting the Tissue Factor (primary initiator of the blood coagulation cascade). These effects can be dangerous for individuals with hemophilia, undergoing surgery, or using blood thinners [R, R, R].
  • Vitamin E and resveratrol can cause widening of the blood vessels (vasodilation) decreasing blood pressure. These effects can be dangerous for individuals with low blood pressure (hypotension) [R, R, R].

Some Genes are Affected by Blueberry Consumption

Anthocyanins from blueberries can alter many genes production (expression) in human fat cells (adipocytes) [R].

The following are some genes affected by blueberry consumption in humans:

  • RBP4 is the main vitamin A transport protein and a fat cell transmission molecule (adipokine) in the liver. Blueberry consumption decreases the concentration of RBP4 in the blood [R].
  • GLUT4 is an insulin dependent glucose transporter. Consumption of blueberries increases insulin sensitivity by producing more glucose transporters (upregulating this gene) [R].
  • Anthocyanins from blueberries enhance the secretion of a fat cell transmission molecule (adipokine) through stimulation of the PPARγ gene [R].
  • SERPINE1 gene produces the protein PAI-1, which promotes blood clotting (thrombosis). Anthocyanins decrease the production of this protein [R].
  • NQO1 is an enzyme that functions as an antioxidant. Consumption of blueberries promotes the production of this gene [R].
  • Some variants of the CYP1B1 gene genotypes are more sensitive to the protective effects of blueberries against DNA damage than other genetic variants [R].

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