Anthocyanins research and health benefit by Ray Sahelian, M.D.
June 22 2014

Anthocyanins are compounds found in plants, particularly berries, that have powerful antioxidant properties. They provide some of the coloring or pigment of plants, flowers and fruits. Next to chlorophyll, anthocyanins are the most important group of plant pigments visible to the human eye. Strawberries have a high content, so do bilberry, blackberry and black currant. Scientists have identified more than 500 different anthocyanins. They are the largest group of water-soluble pigments in the plant kingdom and belong to the family of compounds known as flavonoids.

The color of fruits, vegetables and flowers
Anthocyanins, anthocyanidins, and proanthocyanidins are a large water-soluble pigment group found in a large number of fruits, vegetables and flowers. particularly grapes and berries. These pigments give plants their brilliant colors ranging from pink through scarlet, purple and blue. Scientists have identified several hundred different anthocyanins, including pelargonidin, malvidin, delphinidin, peonidin, and cyanidin, all attached to a sugar molecule. Anthocyanidins are similar to anthocyanins but they do not have a sugar molecule.

Bilberry Extract, also referred to as blueberry, has key bioflavonoids and antioxidants called anthocyanosides, anthocyanins, ellagitannins, and proanthocyanidins. A controlled extraction process guarantees at least 25% anthocyanosides.
Supplement Facts:
Bilberry Fruit Standardized Extract - 80 mg
   (Vaccinium myrtillus)
   Yielding 20 mg anthocyanosides

Bilberry and anthocyanins
Anthocyanosides are the pharmacologically active constituents of bilberries. They consist of a backbone known as anthocyanidin which is bound to one of three sugars: arabinose, glucose, or galactose. Five different anthocyanidins in bilberry produce more than fifteen different anthocyanosides. The fresh fruit contains an anthocyanoside concentration of 0.1 to 0.25 percent. A concentrated bilberry extract however yields 25% anthocyanidin content, which corresponds to about 38% anthocyanosides.

Chemistry
Anthocyanidin plus a sugar molecule leads to an anthocyanin.

Health benefit
Major sources of anthocyanins in the American diet are blueberries, cherries, raspberries, strawberries, black currants, purple grapes and red wine. They have a wide range of biological activities including antioxidant, anti-inflammatory, antimicrobial and anti-cancer activities. In addition they display a variety of effects on blood vessels, platelets and lipoproteins able to reduce the risk of coronary heart diseases.

Blood pressure
Higher anthocyanin intake is associated with lower arterial stiffness and central blood pressure in women.  American Journal of Clinical Nutrition, 2012.

Anthocyanins and cancer
These substances, which give color to most red, purple and blue fruits and vegetables, may help protect against colon cancer and other types of cancer. Bilberry extract is effective at inhibiting the growth of HL60 human leukemia cells and HCT116 human colon carcinoma cells in vitro.

Potential mechanisms of cancer chemoprevention by anthocyanins.
Curr Mol Med. 2003.
Anthocyanins are the chemical components that give the intense color to many fruits and vegetables, such as blueberries, red cabbages and purple sweet potatoes. Epidemiological investigations have indicated that the moderate consumption of anthocyanin products such as red wine or bilberry extract is associated with a lower risk of cardiovascular disease and improvement of visual functions. Recently, there is increasing interesting in the pharmaceutical function of anthocyanins. This review summarizes current knowledge on the various molecular evidences of cancer chemoprevention by anthocyanins. These mechanisms can be subdivided into the following aspects: 1) the antioxidation; 2) the molecular mechanisms involved in anticarcinogenesis; 3) the molecular mechanisms involved in the apoptosis induction of tumor cells. Finally, the bioavailability and structure-activity relationship of anthocyanins are also summarized.

Cholesterol and blood lipids
Anthocyanins have been shown to exert benefits on the lipid profile in many animal models. In one study, a total of 120 subjects (age 4065 y) with high lipid levels were given 160 mg anthocyanins twice daily or placebo for 12 wk in a double-blind, randomized, placebo-controlled trial. Supplementation in humans decreased LDL cholesterol level and increased HDL-cholesterol concentrations. These benefits may be due to the inhibition of plasma cholesteryl ester transfer protein. Am J Clin Nutrition 2009.

Colon Cancer
Effects of commercial anthocyanin-rich extracts on colonic cancer and nontumorigenic colonic cell growth.
J Agric Food Chem. 2004.
Commercially prepared grape (Vitis vinifera), bilberry (Vaccinium myrtillus), and chokeberry (Aronia meloncarpa) anthocyanin-rich extracts (AREs) were investigated for their potential chemopreventive activity against colon cancer. The growth of colon-cancer-derived HT-29 and nontumorigenic colonic NCM460 cells exposed to semipurified AREs (10-75 microg of monomeric anthocyanin/mL) was monitored for up to 72 h using a sulforhodamine B assay. All extracts inhibited the growth of HT-29 cells, with chokeberry ARE being the most potent inhibitor. HT-29 cell growth was inhibited approximately 50% after 48 h of exposure to chokeberry ARE. Most importantly, the growth of NCM460 cells was not inhibited at lower concentrations of all three AREs, illustrating greater growth inhibition of colon cancer, as compared to nontumorigenic colon cells. Extracts were semipurified and characterized by high-pressure liquid chromatography, spectrophotometry, and colorimetry. Grape anthocyanins were the glucosylated derivatives of five different anthocyanidin molecules, with or without p-coumaric acid acylation. Bilberry contained five different anthocyanidins glycosylated with galactose, glucose, and arabinose. Chokeberry anthocyanins were cyanidin derivatives, monoglycosylated mostly with galactose and arabinose. The varying compositions and degrees of growth inhibition suggest that the anthocyanin chemical structure may play an important role in the growth inhibitory activity of commercially available AREs.

Eye health, vision
Anthocyanins Protect Against A2E Photooxidation and Membrane Permeabilization in Retinal Pigment Epithelial Cells.
Photochem Photobiol. 2005
The pyridinium bisretinoid A2E, an autofluorescent pigment that accumulates in retinal pigment epithelial cells with age and in some retinal disorders, can mediate a detergent-like perturbation of cell membranes and light-induced damage to the cell. The photodynamic events initiated by the sensitization of A2E include the generation of singlet oxygen and the oxidation of A2E at carbon-carbon double bonds. To assess the ability of plant-derived anthocyanins to modulate adverse effects of A2E accumulation on RPE cells, these flavylium salts were isolated from extracts of bilberry. Nine anthocyanin fractions reflecting monoglycosides of delphinidin, cyanidin, petunidin and malvidin were obtained and all were shown to suppress the photooxidation of A2E, at least in part, by quenching singlet oxygen. The anthocyanins tested exhibited antioxidant activity of variable efficiency. Cells that had taken up anthocyanins also exhibited a resistance to the membrane permeabilization that occurs as a result of the detergent-like action of A2E.

Anthocyanosides of Vaccinium myrtillus (bilberry) for night vision--a systematic review of placebo-controlled trials.
Surv Ophthalmol. 2004.
We have systematically reviewed placebo-controlled trials of V. myrtillus-extracted anthocyanosides for evidence of positive effects on night vision. Searches of computerized databases and citations in retrieved articles identified 30 trials with outcome measures relevant to vision in reduced light. Of these, 12 were placebo-controlled. The 4 most recent trials were all randomized controlled trials (RCTs) and were negative in outcome. A fifth RCT and 7 non-randomized controlled trials reported positive effects on outcome measures relevant to night vision. Negative outcome was associated with more rigorous methodology but also with lower dose level and extracts from geographically distinct sources that may differ in anthocyanoside composition. Healthy subjects with normal or above average eyesight were tested in 11 of the 12 trials. The hypothesis that V. myrtillus anthocyanosides improves normal night vision is not supported by evidence from rigorous clinical studies. There is a complete absence of rigorous research into the effects of the extract on subjects suffering impaired night vision due to pathological eye conditions. Evidence from methodologically weaker trials and auxiliary evidence from animal studies, trials of synthetic anthocyanosides, and a recent randomized controlled trial of Ribes nigrum (black currant) anthocyanosides may warrant further trials of V. myrtillus anthocyanosides in subjects with impaired night vision.

Q. How good are anthocyanins in eyesight protection?
   A. In my opinion they are good molecules for eyesight health, but there are many flavonoids, carotenoids and other compounds, such as fish oils, which are necessary for optimal vision.

Gastritis
Inhibition of Helicobacter pylori in vitro by various berry extracts, with enhanced susceptibility to clarithromycin.
Mol Cell Biochem. 2004.
Department of Pediatrics, Creighton University Health Sciences Center, Omaha, NE
The objective of this study was to evaluate the effects of various berry extracts, with and without clarithromycin on Helicobacter pylori. Resistance to clarithromycin by H. pylori has been reported, leading to interest in alternatives/adjuncts to therapy with clarithromycin. H. pylori American type culture collection (ATCC) strain 49503 was grown, cell suspensions were made in PBS and diluted 10-fold. One hundred microL of the suspension was then incubated for 18 h with extracts of raspberry, strawberry, cranberry, elderberry, blueberry, bilberry, and OptiBerry, a blend of the six berries. Serially diluted cell suspensions were exposed to clarithromycin. All berry extracts significantly inhibited H. pylori, compared with controls, and also increased susceptibility of H. pylori to clarithromycin, with OptiBerry demonstrating maximal effects.

Leukemia
Induction of apoptosis in cancer cells by Bilberry (Vaccinium myrtillus) and the anthocyanins.
J Agric Food Chem. 2003.
Among ethanol extracts of 10 edible berries, bilberry extract was found to be the most effective at inhibiting the growth of HL60 human leukemia cells and HCT116 human colon carcinoma cells in vitro. Bilberry extract induced apoptotic cell bodies and nucleosomal DNA fragmentation in HL60 cells. Of the extracts tested, that from bilberry contained the largest amounts of phenolic compounds, including anthocyanins, and showed the greatest 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity. Pure delphinidin and malvidin, like the glycosides isolated from the bilberry extract, induced apoptosis in HL60 cells. These results indicate that the bilberry extract and the anthocyanins, bearing delphinidin or malvidin as the aglycon, inhibit the growth of HL60 cells through the induction of apoptosis. Only pure delphinidin and the glycoside isolated from the bilberry extract, but not malvidin and the glycoside, inhibited the growth of HCT116 cells.

Parkinson's disease
A study, funded by the U.S. National Institutes of Health, shows anthocyanins may offer protection against Parkinson's disease in both men and women. Dr. Xiang Gao, an instructor in medicine at Harvard Medical School recommends 2 cups of berries a week. For the study, Dr. Xiang Gao collected data on over 49,000 men who took part in the Health Professionals Follow-up Study and more than 80,000 women from the Nurses' Health Study. Over 22 years of follow-up, 800 people developed Parkinson's disease. Those who consumed the most anthocyanins had a lower risk. Dr. Carlos Singer, a professor of neurology at the University of Miami's Miller School of Medicine, and an expert in Parkinson's disease thinks this has to do with an antioxidant effect. Xiang Gao, M.D., Ph.D., instructor in medicine, Harvard Medical School, Boston; Carlos Singer, M.D., professor of neurology, University of Miami Miller School of Medicine; presentation, American Academy of Neurology's 63rd Annual Meeting, Honolulu, 2011.

Sickle cell disease
Perhaps they can be helpful in reducing symptoms of those afflicted with sickle cell? Would eating berries be of benefit?

Absorption and distribution
When absorbed into the bloodstream from food, anthocyanins can accumulate in tissues, including the liver, eye, and brain.

Intake and daily consumption
The intake of anthocyanins in humans has been estimated to be 180 to 200 mg/day in the US, which is much higher than the intake (25 mg/day) of other flavonoids, including quercetin, kaempferol, myricetin, apigenin, and luteolin.

Black raspberries
Several anthocyanins are present in black raspberries: cyanidin 3-sambubioside, cyanidin 3-glucoside, cyanidin 3-xylosylrutinoside, cyanidin 3-rutinoside, and pelargonidin 3-rutinoside.

Cherry
Cherries contain bioactive anthocyanins that are reported to possess antioxidant, anti-inflammatory, anticancer, antidiabetic and antiobese properties. Red sweet cherries contained cyanidin-3-O-rutinoside as a major anthocyanin (>95%).

Anthocyanins in barley, a cereal grain
Anthocyanin composition and oxygen radical scavenging capacity (ORAC) of milled and pearled purple, black, and common barley.
J Agric Food Chem. 2009. Department of Food Science, University of Manitoba, Winnipeg, Manitoba, Canada.
This study investigated the antioxidant capacity and anthocyanin composition of a bran-rich pearling fraction (10% outer kernel layers) and whole kernel flour of purple, black, and yellow barley genotypes. HPLC analysis showed that as much as 6 times more anthocyanin per unit weight (microg/g) was present in the bran-rich fractions of yellow and purple barley than in their corresponding whole kernel flours. Antioxidant activity analysis showed that the ORAC values for the bran-rich fractions were significantly higher than for the whole kernel flour.

Anthocyanin Research studies, antioxidant
Inhibition of protein and lipid oxidation in liposomes by berry phenolics.
J Agric Food Chem. 2004.
The antioxidant activity of berry phenolics such as anthocyanins, ellagitannins, and proanthocyanidins from raspberry (Rubus idaeus), bilberry (Vaccinium myrtillus), lingonberry (Vaccinium vitis-idaea), and black currant (Ribes nigrum) was investigated in a lactalbumin-liposome system. The extent of protein oxidation was measured by determining the loss of tryptophan fluorescence and formation of protein carbonyl compounds and that of lipid oxidation by conjugated diene hydroperoxides and hexanal analyses. The antioxidant protection toward lipid oxidation was best provided by lingonberry and bilberry phenolics followed by black currant and raspberry phenolics. Bilberry and raspberry phenolics exhibited the best overall antioxidant activity toward protein oxidation. Proanthocyanidins, especially the dimeric and trimeric forms, in lingonberries were among the most active phenolic constituents toward both lipid and protein oxidation. In bilberries and black currants, anthocyanins contributed the most to the antioxidant effect by inhibiting the formation of both hexanal and protein carbonyls. In raspberries, ellagitannins were responsible for the antioxidant activity. While the antioxidant effect of berry proanthocyanidins and anthocyanins was dose-dependent, ellagitannins appeared to be equally active at all concentrations. In conclusion, berries are rich in monomeric and polymeric phenolic compounds providing protection toward both lipid and protein oxidation.

Products, various dietary supplements sold over the counter
Anti-angiogenic, antioxidant, and anti-carcinogenic properties of a novel anthocyanin-rich berry extract formula.
Biochemistry (Mosc). 2004. Department of Pharmacy Sciences, Creighton University Medical Center, Omaha, NE
Edible berry anthocyanins possess a broad spectrum of therapeutic and anti-carcinogenic properties. Berries are rich in anthocyanins, compounds that provide pigmentation to fruits and serve as natural antioxidants. Anthocyanins repair and protect genomic DNA integrity. Earlier studies have shown that berry anthocyanins are beneficial in reducing age-associated oxidative stress, as well as in improving neuronal and cognitive brain function. Six berry extracts (wild blueberry, bilberry, cranberry, elderberry, raspberry seeds, and strawberry) were studied for antioxidant efficacy, cytotoxic potential, cellular uptake, and anti-angiogenic (the ability to reduce unwanted growth of blood vessels, which can lead to varicose veins and tumor formation) properties. We evaluated various combinations of edible berry extracts and developed a synergistic formula, OptiBerry IH141, which exhibited high ORAC (Oxygen-Radical Absorbing Capacity) value, low cytotoxicity, and superior anti-angiogenic properties compared to the other combinations tested. Anti-angiogenic approaches to treat cancer represent a priority area in vascular tumor biology. OptiBerry significantly inhibited both H2O2- and TNF-alpha-induced VEGF (Vascular Endothelial Growth Factor) expression by human keratinocytes. VEGF is a key regulator of tumor angiogenesis. Matrigel assay using human microvascular endothelial cells showed that OptiBerry impaired angiogenesis. In an in vivo model of angiogenesis, OptiBerry significantly inhibited basal MCP-1 and inducible NF-kappaB transcriptions. Endothelioma cells pretreated with OptiBerry showed a diminished ability to form hemangioma and markedly decreased tumor growth by more than 50%. In essence, these studies highlight the novel anti-angiogenic, antioxidant, and anti-carcinogenic potential of a novel anthocyanin-rich berry extract formula, OptiBerry.

Structural and functional characterization of polyphenols isolated from acerola (Malpighia emarginata) fruit.
Biosci Biotechnol Biochem. 2005.
Two anthocyanins, cyanidin-3-alpha-O-rhamnoside (C3R) and pelargonidin-3-alpha-O-rhamnoside (P3R), and quercitrin, were isolated from acerola (Malpighia emarginata DC.) fruit. These polyphenols were evaluated based on the functional properties associated with diabetes mellitus or its complications, that is, on the radical scavenging activity and the inhibitory effect on both alpha-glucosidase and advanced glycation end product (AGE) formation. C3R and quercitrin revealed strong radical scavenging activity. While the inhibitory profiles of isolated polyphenols except quercitrin towards alpha-glucosidase activity were low, all polyphenols strongly inhibited AGE formation.

Mulberry anthocyanins, cyanidin 3-rutinoside and cyanidin 3-glucoside, exhibited an inhibitory effect on the migration and invasion of a human lung cancer cell line.
Cancer Lett. 2005.
In this study, we first observed that cyanidin 3-rutinoside and cyanidin 3-glucoside ( extracted from mulberry ) exerted a dose-dependent inhibitory effect on the migration and invasion, of highly metastatic A549 human lung carcinoma cells in absence of cytotoxicity. Our result suggested that anthocyanins from mulberry could decrease the in vitro invasiveness of cancer cells and therefore, may be of great value in developing a potential cancer therapy.

The acai berry also has a high content of anthocyanins. Anthocyanins are common ingredients of human diet, and the rich source of them are: aronia fruits, black currant, raspberry, grapes and apples. Because of their chemical structure they are able to influence many active substances in human body having antioxidative, antiinflammatory and cardioprotective activity.

Questions
 

Q. Do anthocyanins help with sexual enhancement?
   A. I'm not sure but I think they could help dilate blood vessels.

Q. I am a health food store owner and received an email that said: Introducing CYAN-X, the multi anthocyanin extract, from United Nutrition. CYAN-X multi anthocyanins is a proprietary powder blend of berries and frui. Anthocyanins are versatile flavonoid pigments found in red and purple fruits and vegetables, including cabbage, beets, blueberries, cherries, raspberries and grapes. Anthocyanins are associated as potent antioxidants with health benefits related to cardiovascular disease, eye health, as an anti-inflammatory and overall health. What is your opinion of this CYAN-X product?
   A. Anthocyanins are beneficial substances but I am not aware of specific research with this proprietary blend.

I can't find the daily recommendation intake of anthocyanin. Is it 180 to 200 mg / day? How much is recommended for our daily consumption? Any harmful effect for overdoes?
    There is no RDA for anthocyanin intake and little research is available as to the maximum safe intake.