Archive for the ‘anthocyanins’ Category

Fruits and Vegetables are good for you! Wow… Shazam… how much university research did it take them to figure THAT ONE out? We all KNOW that they are good for us… But once again, how many of us EAT that way? Not many… not many… This is why it is imperative to keep MEDOX in your arsenal! It is ALL NATURAL folks… nothing like those synthetic vitamins made in a lab by some drug company… 

This is what is great about Medox… lots of people ask… well why is it Darkish purply blue?  Simple.  It is MADE from billberries and black currants! Enough said… oh and this is a great article about trying to color foods with NATURAL anthocyanins…  Coloring

Jean Perrins wrote a great blog post on Anthocyanins. She really nailed it on the head for the current research on berries like what is found in Medox!Here is her blog post.   

Raul G Corredor MD 

Copyrigths: Purelife Scandinavia, Raul G Corredor 2007 

 

The advantages of an antioxidative diet are well accepted today. However, new 

research shows that  the term antioxidant is far from being specific. Thought 

antioxidants are present in many foods including wines, fruits, nuts, olive oil, 

cocoa, honey, some vegetables, green tea and cereals, dietary supplements 

(including vitamins E, C or A), oligoelements (like zinc and selenium), and 

carotenoids (like beta carotene, lutein and zeaxanthin), new biological and 

chemical characteristics of this compounds have been discovered indicating  that 

there are different types of antioxidants, some of them with different free-radical 

scavenging capacities (indicating their potency), and even more important, with 

different mechanisms of action.  

 

Description: One important family among antioxidants is the flavonoid group, 

which comprise the most abundant group of plant polyphenols. The flavonoid 

group includes the anthocyanins, the flavonols, the flavones, the flavanones, the 

proanthocyanidines, the flavan-3-ols and isoflavones. From these, anthocyanins 

have received special attention because a long tradition of beneficial effects. 

Thought other antioxidants have been tested in clinical trials that have given 

conflicting results; new research has been done recently and clinical trials are 

ongoing to test the specific effect of anthocyanins  in vitro and in vivo.  MEDOX 

(also identified as MP865) is a unique combination of anthocyanins obtained by 

purification from black currants (Ribes nigrum L.) and from bilberries (Vaccinium 

myrtillus). The purification process (MEDOX is made in an in-house developed, 

high tech., patented, chromatographic process) yields highly purified 

anthocyanines presented as capsules of 80 mg pure anthocyanins plus 115 mg 

polyphenols. Next, scientific evidence demonstrating important biological effects 

of specific anthocyanins (as well as the synergistic effect of the natural 

anthocyanin mixture) that compose MEDOX is presented.  

 

Absorption and metabolism: Anthocyanins are hydro-soluble plant pigments 

that usually have an attached sugar (glycosides) or les frequently, do not have it 

(aglycones).  Both forms have particular characteristics in reference to absorption 

and antioxidant capabilities. Although some generalizations are possible, new 

evidence suggest that the biological properties are different, and some times 

unique, among different anthocyanines (for review see Prior et al. 2006). As an 

example, now it is accepted that anthocyanines can be absorbed intact as 

glycosides (in contraposition to other hydro-soluble compounds), though still the 

aglycones present easier absorption. Several mechanisms are involved in 

absorption to explain why anthocyanines can be detected in plasma as soon as 6 

minutes after ingestion, and the maximum concentration in plasma (Cmax) can 

be reached 30 to 120 minutes after ingestion (Prior 2006). Surprisingly, one of 

those mechanisms has been determined to be direct gastric absorption using a 

bilitraslocase-type enzyme (Passamonti  2003) at the gastric mucosa; the highest 

absorption seems to be at the jejunum. Thought the absorbed fraction of  

anthocyanins, determined by measuring plasma levels and excretion, is around 

0.1 (1%), the process of absorption and metabolism is still under active 

investigation. In particular, the fraction of anthocyanins that is collected in feces 

after ingestion, has turned out to be very important because this fraction 

comprise intact anthocyanins and metabolized anthocyanins excreted in the bile 

together with phenolic acids which are products of bacterial degradation. This 

mixture is biologically active and is responsible for the reported protective 

antioxidant effect over colonic mucosa mediated by inhibition of malignant 

transformation and/or invasion (Coates 2007, Cooke 2006, Prior 2006). The most 

abundant anthocyanins in blackcurrants are Cyanidin-3-rutinoside, Delphinidin-3- 

rutinoside, Delphinidin-3-glucoside and Cyanidin-3-glucoside and their aglycones 

cyanidin and delphinidin (Slimestad and Solheim 2002, Prior 2006). The most 

abundant anthocyanins in bilberries are, in order of percentage composition,  

Delphinidin-3-galactoside, Delphinidin-3-glucoside, Delphinidin-3-arabinoside, 

Cyanidin-3-glucoside, Cyanidin-3-galactoside, Cyanidin-3-arabinoside, Malvidin- 

3-glucoside, Petunidin-3-glucoside, Malvidin-3-galactoside, Petunidin-3- 

galactoside, Peonidin-3-glucoside, Petunidin-3-arabinoside, Malvidin-3- 

arabinoside, Peonidin-3-galactoside and Peonidin-3-arabinoside (Rahman 2006, 

Cooke 2006(b)). This composition gives MEDOX unique characteristics, not only 

for the highly purified amount of anthocyanins, but also because the superoxide 

radical-scavenging activity is synergic among different anthocyanins (Rahman 

2006). Anthocyanins from bilberries and black currants (which are the prime 

material in MEDOX) are rapidly absorbed after ingestion (facilitated by specific 

transporters and the aglycone part), Keep their antioxidant ability during the 

process (reinforced in part by the stability of the rutenoside compounds 

(Rubinskiene 2005)), and have a longer half life in human plasma due to the 

presence of glycosides which are metabolized in part to anthocyanidins, which 

are suspected to exert even more potent biological activities (Cooke 2006, Cooke 

2006(b). The last feature is particularly important because is an in vivo 

demonstration about the presence of aglycones in human plasma which can then 

undergo further biotransformation, asseveration that has been subject of 

controversy.  

 

Antioxidant activity: The antioxidant properties of anthocyanins have been 

extensively demonstrated in vivo and in vitro and only specific mechanisms are 

considered here. In addition to the higher superoxide-scavenging activity and 

peroxynitrite-scavenging activity in the natural or reconstituted mix of 

anthocyanins (Rahman 2006); other biological effects of anthocyanins have been 

demonstrated, some of which are not directly related to their antioxidant capacity. 

Below, some of those effects will be described.  

 

Aging and exercise-induced oxidative stress: Starting with the general 

antioxidant ability of anthocyanins, some human studies can be cited. In one 

study, healthy volunteers received berry juice or the same juice after 

anthocyanins-polyphenols extraction during three weeks; during intervention with 

the fruit juice blood and urine samples were collected; a decrease of oxidative 

DNA damage (p<5×10(-4) (determined by the comet assay) and an increase of 

reduced glutathione (p<5×10(-4)) and of glutathione status (p<0.05) were 

observed (Weisel 2006). Elevation of glutathione S-transferase P1 (hGSTP1) 

protein expression in human leucocytes of healthy volunteers has also been 

demonstrated after two two-weeks period of berry juice consumption when 

compared with controls; hGSTP1 has been shown to prevent DNA damage and 

mutagenesis (Hofmann 2006). Interestingly, in vitro polyphenol mixtures up- 

regulated other biotransformation enzymes (e. g., members of the cytochrom 

P450 and the sulphotransferase family) and treatment of leucocytes led to a 

modulated mRNA expression of selected genes, not directly related to oxidative 

defense systems (Hofmann 2006). According to another study, this antioxidant 

protection seems to be extended in individuals performing physical exercise as 

determined by analyzing the levels of lipid peroxidation (TBARS) in blood 

samples from rowers (with or without berry juice supplementation) performing a 

daily physical exercise during 1 month training camp. In the group supplemented 

with berry juice, glutathione peroxidase activity was lower in the samples 

collected 1 min after the exercise test, superoxide dismutase activity was lower in 

the samples taken following a 24-h recovery, and TBARS were lower at both 

times when compared to the subjects receiving placebo. The authors of this 

study suggest that an increased intake of anthocyanins limits the exercise- 

induced oxidative damage to red blood cells, most probably by enhancing the 

endogenous antioxidant defense (Pilaczynska-Szczesniak 2005). The protection 

against exercise-induced oxidative damage is further supported by a double- 

blind, placebo-controlled, crossover study that assesses peripheral circulation 

using near-infrared spectroscopy (NIRS). Forearm blood flow (FBF) is measured 

after venous occlusion prior to and hourly for 4 h after ingestion of blackcurrant 

anthocyanins (BCA). FBF increases significantly 2 h after BCA ingestion [BCA 

1.22 (0.13)-fold increase relative to pre-values vs. placebo 0.83 (0.06) of pre- 

values; P < 0.05] and then tended to increase for a further 3 h after ingestion 

[BCA 1.26 (0.15)-fold increase relative to pre-values vs. placebo 0.82 (0.07) of 

pre-values; P = 0.078].  The protective effect is also observed if intermittent 

typing workload is performed for 30 min in order to induce acute shoulder 

stiffness. BCA intake prevented the decrease in oxy-Hb significantly (P < 0.05), 

and also tended to alleviate the increase in root mean square (RMS) of the EMG 

during the typing workload and muscle stiffness after the workload, in this way, 

reducing muscle fatigue (Matsumoto 2005). 

 

Anti-inflammatory activity: The mechanisms mediating the anti-inflammatory 

effect of anthocyanins are under continuous investigation.  It has been shown 

that anthocyanins have ability to inhibit cyclooxygenase-2 (COX-2) at the same 

amount that NSAIDs do (Seeram 2001). Among the molecular mechanisms 

involved in this response it has been shown in murine lipopolysaccharide- 

activated macrophages,  that anthocyanidins, specially Delphinidin, suppressed 

COX-2 by blocking the mitogen-activated protein kinase (MAPK) pathway, with 

simultaneous modulation of the nuclear factor-kB (NF-kB) pathway, activator 

protein-1 (AP-1) and C/EBP? (Hou 2005). Other related anti-inflammatory 

mechanisms have been invoked, including inhibition of interleukin-6 related also 

with inhibition of the NF-kB pathway (Omoigui 2007); and the modulatory effect in 

tumor necrosis factor-? (TNF-?) (Xu J-W 2006). A clinical study showed that 

proanthocyanidins reduced inflammation and oxidative stress plasma levels and 

adhesion molecules (ICAM-1, VCAM-1 and E-selectin) in systemic sclerosis 

(Kalin 2002). 

 

Cardiovascular System: In reference to the cardiovascular system it is clear 

now that atherosclerosis is an inflammatory disorder; also that lipid peroxidation 

as well as alterations in nitric oxide-mediated vasodilatation are relevant 

pathogenic events. This circumstances put anthocyanins in a privileged position 

since they are able to positively influence all three factors.  Xia et al. (Xia 2007) 

reported a novel mechanism how anthocyanins can attenuate atherosclerotic 

plaque formation in apolipoprotein E (ApoE)-deficient mice. It has been published 

that hyperactivation of the pro-inflammatory CD40 receptor is greatly amplified by 

hipercholesterolemia and other pro-inflammatory stimulus including its ligation to 

CD40 ligand (CD40L) and traslocation of tumor necrosis factor receptor- 

associated factors (TRAF-2) to the membrane (Lutgens 2000,Frolov and Hui 

2007); CD40 activation strongly depends on the cholesterol domain (raft) 

structure of the cell plasma membrane. Xia et al showed that anthocyanins, 

specifically Cyanidin-3-glucoside or peonidin-3-glucoside, reduced raft 

cholesterol levels by up-regulation of ABCA1-mediated cholesterol efflux to Apo 

A-I, in this way, inhibiting the formation of a CD40/TRAF-2 complex (formed after 

traslocation of TRAF-2 to the lipid raft) able to activate NF-kB and inhibiting also 

subsequent up-regulation of pro-inflammatory citokines IL-1, IL-8 and monocyte 

chemoattractant protein-1 (MCP-1) in human endothelial cells. Te authors 

conclude that anthocyanin protects from CD40-induced proinflammatory 

signaling by preventing TRAF-2 translocation to lipid rafts through regulation of 

cholesterol distribution (Xia 2007). A positive role of anthocyanins in preventing 

endothelial cell death has been also demonstrated. TNF-? is involved in 

inflammation-mediated vascular damage by inducing apoptosis (associated with 

cleaved caspase-3 and cleaved poly(ADP-ribose) polymerase) of endothelial 

cells. Anthocyanins inhibit this effect of TNF-? through multiple signaling 

pathways which include elevation of endothelial nitric oxide synthase (eNOS) and 

thioredoxin (Trx); this is related to activation of AKT, decrease in lipid 

peroxidation products and modulation of the tumor suppressor gene P53 (Xu J-W 

2006).  It is well accepted that eNOS promote endothelium-dependent relaxation 

of blood vessels, and this is consistent with the vasodilatation produced by 

anthocyanins. Lazze et al (Lazze 2006) showed that anthocyanidins (aglycones 

delphinidin and cyanidin) at the physiological concentration that could be 

observed in vivo, decreased endothelin-1 production and increased endothelial 

nitric oxide synthase in cultured human endothelial cells. As an example of 

anthocyanins diversity, Bell et al (Bell 2006) applied extracts from three different 

berries (bilberry, chokeberry or elderberry) to coronary arterial rings isolated from 

64 pigs. Bilberry and chokeberry extracts, but not elderberry extract, produced 

dose and endothelium-dependent vasorelaxation; at lower concentration bilberry 

and chokeberry extracts did not induce vasorelaxation but protected against 

ROS-induced (pyrogallol-induced) vasoconstricition.  

 

Prevention of malignant transformation: Anthocyanins prevent cellular 

malignant transformation. Moreover, anthocyanins have been probed to induce 

apoptosis in some malignant cells. This characteristic is extremely important 

since, as was shown above, anthocyanins are protective for normal cells. A 

recent publication from Feng et al (Feng 2007) brings light over this apparent 

contradiction and reinforces the selectivity of anthocyanins anti-tumorous activity. 

Feng found that Cyanidin-3-rutenoside selectively kills leukemic cells (HL-60 

cells) by induction of oxidative stress. Anthocyanins induce peroxide 

accumulation and apoptosis in HL-60 cells. In addition, cyanidin-3-rutinoside 

treatment resulted in reactive 

oxygen species (ROS)-dependent activation of p38 MAPK and c-jun NH2- 

terminal kinase (JNK), which contributed to cell death by activating the 

mitochondrial pathway mediated by Bim. Notably, cyanidin-3-rutinoside treatment 

did not lead to 

Increased ROS accumulation in normal human peripheral blood mononuclear 

cells and had no cytotoxic effects on these cells (Feng 2007). Molecular 

mechanisms behind the chemoprotective effects of anthocyanins can be inferred 

from all the biological effects already mentioned. Hou et al (Hou 2004) proposed 

similar mechanisms including modulation of MAPK pathway, AP-1 factor, NF-kB 

pathway, Cyclooxigenase-2 gene and JNK-mediated caspase activation. Though 

more information is available every day; the current information should be 

enough to support the use of anthocyanines. Block et al (Block 2007) performed 

a systematic review of the literature in order to compile results from randomized 

trials that evaluate concurrent use of antioxidants with chemotherapy. 

Anthocyanins were not used in any of this trials. Still, Block et al. concluded that 

the review “ provides suggestive evidence that antioxidant supplementation helps 

reduce some adverse reactions including neurotoxicity, thrombocytopenia, 

diarrhea, thus 

enabling increased or uninterrupted dosing in patients who otherwise may 

discontinue treatment due to side effects”. The review did not detect diminished 

chemotherapeutic efficacy in patients receiving antioxidant supplementation in 

randomized trials and suggest that “the clinical application of antioxidant 

supplementation 

during chemotherapy should be further explored” (Block 2007). The link between 

the inhibitory effect of anthocyanins over the epidermal growth factor receptor 

(EGFR) and their effect on phosphodiesterase modulation, was proposed by 

Marko et al (Marko 2004) to be the common end point modulation of the MAPK 

pathway that regulates cell proliferation. 

 

The visual system: The eye is a biological system relying significantly in 

pigment function, and it seems that the anthocyanin pigments have important 

beneficial effects in the eye. It has been shown that bilberry anthocyanins protect 

human retinal pigment ephitelial cells in culture (ARPE-19 cells) from pyridinium 

bisretinoid (A2E) photooxidation and membrane permeabilization; A2E is a 

pigment that accumulates in retinal pigment epithelial cells with age and also in 

“Stargardt” and “Best” retinal disorders, A2E mediate a detergent-like 

permeabilization of cell membranes and light-induced damage. Anthocyanines 

quenched singlet oxygen which mediated the photooxidation process and 

improved survival of RPE cells by 60% (Jang 2005). The effects of anthocyanin- 

enriched bilberry extracts were also analyzed in ARPE-19 cells oxidatively 

challenged with hydrogen peroxide. The same extract after phenolic removal was 

used as control.  Anthocyanines from bilberry up-regulated the oxidative stress 

defensive enzymes Heme Oxygenase-1 and Glutation S-Transferase-pi. 

Indicating this way, that anthocyanins have effect in gene expression of cell- 

endogenous antioxidant mediators (Milbury 2007). In the rd1 mouse model of 

retinitis pigmentosa (RP) a cocktail of antioxidants (not including anthocyanins) 

was administered. Carbonyl adducts and 

immunohistochemical staining for acrolein were measured as markers for 

oxidative damage. “the staining for acrolein in remaining cones at day 35 of life 

was eliminated in antioxidant-treated rd1 mice, confirming that the treatment 

markedly reduced oxidative damage in cones; this was accompanied by a 2-fold 

increase in cone cell density and a 50% increase in medium-wavelength cone 

opsin mRNA. Antioxidants also caused some preservation of cone function 

based upon photopic electroretinograms”(Komeima 2006). 

 

Neuroprotection: Finally, it is important to mention the possible role of 

anthocyanins in the brain. 6-hydroxy dopamine is a neurotoxic metabolite of 

dopamine. Both can be oxidized to generate ROS, which has been implicated in 

dopaminergic neurodegeneration; this could be also related to abnormal redox 

state and cytoplasmic release of cytocrhome c (Cytc) leading to neuronal 

apoptosis. Purified anthocyanins and Vaccinium extracts were tested for their 

effect to protect against Cytc-enhanced 6-hydroxy DA oxidation. The most potent 

protector was Vaccinium myrtillus (bilberry) with a 50% inhibition (Yao 2007). 

This study provide strong support for testing anthocyanins as neuronal and 

mitochondrial protectors. 

 

At this point, it could be undoubtedly concluded that there is a big amount of 

evidence about the biological mechanisms mediating the beneficial effects of  the 

anthocyanins that compose MEDOX.  MEDOX provides a unique opportunity to 

supplement high quality anthocyanins.  

 

References 

 

Bagchi D., Sen C. K., Bagchi M. and Atalay M.. REVIEW:  

Anti-angiogenic, Antioxidant, and Anti-carcinogenic Properties of a  

Novel Anthocyanin-Rich Berry Extract Formula. Biochemistry (Moscow)  

2004; 69(1): 75-80. 

 

Bell D. R. and Gochenaur  K. Direct vasoactive and vasoprotective properties 

of anthocyanin-rich extracts. J Appl Physiol. 2006; 100: 1164–1170. 

 

Block K. I., Koch M. C., Mead M. N.,  M. N., Tothy P. K., 

Newman R. A., Gyllenhaal C. Impact of antioxidant supplementation on 

chemotherapeutic efficacy: A systematic review of the evidence from 

randomized controlled trials. Cancer Treat Rev. 2007 

doi:10.1016/j.ctrv.2007.01.005 

 

Coates E. M., Popa G., Gill C. IR., McCann M. J., McDougall G. J., Stewart D. 

and Rowland I. Colon-available raspberry polyphenols exhibit anti-cancer 

effects on in vitro models of colon cancer Journal of Carcinogenesis. 2007; 

6:4 

 

Cooke  D., Schwarz  M., Boocock D., Winterhalter P., Steward W. P., Gescher A. 

J., Marczylo T. H. Effect of cyanidin-3-glucoside and an anthocyanin mixture 

from bilberry on adenoma development in the ApcMin mouse model of 

intestinal carcinogenesis - Relationship with tissue anthocyanin levels. 

International Journal of Cancer.  2006; 119(9): 2213-2220. 

 

Cooke D. N., Thomasset S., Boocock D. J., Schwarz M., Winterhalter P., 

Steward W. P., Gescher A. J. and Marczylo T. H. Development of Analyses by 

High-Performance Liquid Chromatography and Liquid 

Chromatography/Tandem Mass Spectrometry of Bilberry ( Vaccinium 

myrtilus) Anthocyanins in Human Plasma and Urine J. Agric. Food Chem. 

2006; 54: 7009-7013. 

 

Feng R., Ni H., Wang S. Y., Tourkova I. L., Shurin M. R., Harada H. and Yin X. 

Cyanidin-3-rutinoside, a Natural Polyphenol Antioxidant, Selectively Kills 

Leukemic Cells by Induction of Oxidative Stress. The journal of biological 

chemistry. 2007; 282(18): 13468–13476. 

 

Frolov A. and Hui D. Y. The modern art of atherosclerosis: A picture of 

colorful plants, cholesterol, and inflammation. Arterioscler. Thromb. Vasc. 

Biol. 2007; 27: 450-452. 

 

Hofmann T., Liegibel  U., Winterhalter  P., Bub A., Rechkemmer G., Pool-Zobel  B. 

L. Intervention with polyphenol-rich fruit juices results in an elevation of 

glutathione S-transferase P1 (hGSTP1) protein expression in human 

leucocytes of healthy volunteers. Molecular Nutrition & Food Research. 2006; 

50(12): 1191–1200. 

 

Hou D., Yanagita T., Uto T., Masuzaki S., Fujii M. Anthocyanidins inhibit 

cyclooxygenase-2 expression in LPS-evoked macrophages: Structure– 

activity relationship and molecular mechanisms involved. Biochemical 

Pharmacology. 2005;  70: 417–425. 

 

Hou D., Fujii M., Terahara N., and Yoshimoto M. Molecular Mechanisms 

Behind the Chemopreventive Effects of Anthocyanidins. J Biomed 

Biotechnol. 2004; 5: 321–325. 

 

Jang Y. P., Zhou J., Nakanishi K. and Sparrow J. R. Anthocyanins Protect 

Against A2E Photooxidation and Membrane Permeabilization in Retinal 

Pigment Epithelial Cells. Photochem Photobiol. 2005; 81(3): 529–536. 

 

Kalin R., Righi A., Del-Rosso A., Bagchi D., Generini S., Cerinic M. M., Das D. K. 

Activin, a grape seed-derived proanthocyanidin extract, reduces plasma 

levels of oxidative stress and adhesion molecules (ICAM-1, VCAM-1 and E- 

selectin) in systemic sclerosis. Free-Radic-Res. 2002; 36(8): 819-25. 

 

Komeima K., Rogers B. S., Lu L. and Campochiaro P. A. Antioxidants reduce 

cone cell death in a model of retinitis pigmentosa. PNAS. 2006; 103(30): 

11300-11305. 

 

Lazze M. C., Pizzala R., Perucca P., Cazzalini1 O., Savio M., Forti L., Vannini1 

V. and Bianchi L. Anthocyanidins decrease endothelin-1 production and 

increase endothelial nitric oxide synthase in human endothelial cells Mol. 

Nutr. Food Res. 2006; 50: 44–51. 

 

Lutgens E., Cleutjens K. B., Heeneman S., Koteliansky V. E., Burkly L. C., 

Daemen M. J. Both early and delayed anti-CD40L antibody treatment 

induces a stable plaque phenotype. Proc Natl Acad Sci U S A. 2000; 97: 7464- 

7469. 

 

Marko  D., Puppel N., Tjaden Z., Jakobs S., Pahlke G. The substitution pattern 

of anthocyanidins affects different cellular signaling cascades regulating 

cell proliferation. Molecular Nutrition & Food Research. 2004; 48(4): 318–325. 

 

Matsumoto H., Takenami E., Iwasaki-Kurashige K., Osada T., Katsumura T. and 

Hamaoka T. Effects of blackcurrant anthocyanin intake on peripheral 

muscle circulation during typing work in humans. Eur J Appl Physiol. 2005; 

94: 36–45. 

 

Milbury P. E., Graf B., Curran-Celentano J. M. and Blumberg J. B. Bilberry 

(Vaccinium myrtillus) Anthocyanins modulate Heme Oxygenase-1 and 

Glutathione-S-Transferase-pi expression in ARPE-19 cells. Invest Ophtalmol 

Vis Sci.  2007; 48(5): 2343-2349. 

 

Nakajima J., Tanaka I., Seo S., Yamazaki M. and Saito K. LC/PDA/ESI-MS 

Profiling and Radical Scavenging Activity of Anthocyanins in Various 

Berries. Journal of Biomedicine and Biotechnology. 2004; 5:241–247 

 

Omoigui S. The interleukin-6 inflamation pathway from cholesterol to aging- 

role of statins, biphosphonates and plant polyphenols in aging and age- 

related diseases. Immunity & Ageing. 2007; 4: 1. 

 

Passamonti S., Vrhovsek U., Vanzo A., Mattivi F. The stomach as a site for 

anthocyanins absorption from food. FEBS Lett. 2003; 544(1-3): 210-3. 

 

Pilaczynska-Szczesniak L., Skarpanska-Steinborn A., Deskur E., Basta P., 

Horoszkiewicz-Hassan M. The influence of chokeberry juice supplementation 

on the reduction of oxidative stress resulting from an incremental rowing 

ergometer exercise. Int J Sport Nutr Exerc Metab. 2005;15(1):48-58. 

 

Rubinskiene M., Jasutiene I., Venskutonis P. R., Viskelis P.  HPLC 

determination of the composition and stability of blackcurrant 

anthocyanins.  Journal of Chromatographic Science. 2005; 43(9):478-482. 

 

Seeram N. P., Momin R. A., Nair M. G., Bourqhin L. D. Cyclooxygenase 

inhibitory and antioxidant cyaniding glycosides in cherries and berries. 

Phytomedicine. 2001; 8(5): 362-369. 

 

Weisel T.,  Baum M., Eisenbrand  G., Dietrich H., Will  F.,Stockis J., Kulling  S., 

Rüfer  C., Johannes C., Janzowski C. Dr., An anthocyanin/polyphenolic-rich 

fruit juice reduces oxidative DNA damage and increases glutathione level 

in healthy probands. Biotechnology Journa.l 2006; 1(4): 388-397. 

 

Xia M., Ling W., Zhu H., Wang Q., Ma J., Hou M., Tang Z., Li L., Ye Q. 

Anthocyanins prevents  from CD40-activated proinflammatory signaling in 

endothelial cells by regulating cholesterol distribution. Arterioscler. Thromb. 

Vasc. Bio.l 2007; 27: 519-524. 

 

Xu J-W., Ikeda K., Yamori Y. Inhibitory effect of polyphenol cyanidin on TNF-  

induced apoptosis through multiple signaling pathways in endothelial 

cells. Atherosclerosis 2006, doi:10,1016/j.atherosclerosis.2006.09.006. 

 

Yao Y. and Vieira A. Protective activities of Vaccinium antioxidants with 

potential relevance to mitochondrial dysfunction and neurotoxicity. 

Neurotoxicology. 2007; 28(1):93-100. 

 

 

Copyrigths: Purelife Scandinavia, Raul G Corredor 2007 

What are anthocyanins?

 

In order to give a good, general description of anthocynins, we have chosen to include the article from The December 2001 Issue of Nutrition Science News. This seems to us to be the best survey available as of yet.

 

These plant pigments are more than coloring agents for fruit juices, wine, and other beverages. They also contain an array of health-promoting benefits.

By Marilyn Sterling, R.D.

Eaten in large amounts by primitive humans, anthocyanins are antioxidant flavonoids that protect many body systems. They have some of the strongest physiological effects of any plant compounds, and they are also things of beauty: anthocyanins provide pigment for pansies, petunias, and plums. (Anthocyanins are a separate class of flavonoids from proanthocyanidins, discussed in NSN 2000;5(6):231-4.)

Anthocyanins are the active component in several herbal folk medicines such as bilberry (Vaccinium myrtillus), which was used in the 12th century to induce menstruation and during World War II to improve British pilots’ night vision. Scientists are now discovering how such anthocyanins work and are beginning to appreciate their health benefits.

Anthocyanins link with sugar molecules to form anthocyanins; besides chlorophyll, anthocyanins are probably the most important group of visible plant pigments. Anthocyanins, a flavonoid category, were found in one study to have the strongest antioxidizing power of 150 flavonoids.¹Â (Approximately 4,000 different flavonoids have been identified.)

The U.S. Department of Agriculture recently tested the abilities of berry varieties to protect against oxidative damage. In general, blackberries have the highest antioxidant capacity of any fruit. Different varieties of the same species have varying amounts of anthocyanins. The varietal cultivars with the highest antioxidative capacity against superoxide radicals, hydrogen peroxide, and other oxidants are hull, thornless, and jewel raspberries; early black cranberries; and Elliot blueberries.²

Anthocyanidins and their derivatives, many found in common foods, protect against a variety of oxidants through a number of mechanisms. For example, red cabbage anthocyanins protect animals against oxidative stress from the toxin paraquat.³Cyanidins, found in most fruit sources of anthocyanins, have been found to “function as a potent antioxidant in vivo” in recent Japanese animal studies.⁴ In other animal studies, cyanidins protected cell membrane lipids from oxidation by a variety of harmful substances.^5 Additional animal studies confirm that cyanidin is four times more powerful an antioxidant than vitamin E.⁶ The anthocyanin pelargonidin protects the amino acid tyrosine from the highly reactive oxidant peroxynitrite.⁷ Eggplant contains a derivative of the anthocyanidin delphinidin called nasunin, which interferes with the dangerous hydroxyl radical-generating system—a major source of oxidants in the body.⁸

Diverse Health Effects

Studies show anthocyanins’ positive influences on a variety of health conditions. One reason is their anti-inflammatory properties, which affect collagen and the nervous system. Their ability to protect both large and small blood vessels from oxidative damage derives from a range of effects, including mitigating microvessel damage from high blood-sugar levels that cause complications in diabetics. By the same token, diabetic retinopathy, which damages eyesight, is caused by leaking, damaged capillaries.

Inflammation And Collagen

In the course of inflammation, enzymes damage connective tissue in capillaries, causing blood to leak into surrounding tissues. Oxidants are released and further damage blood-vessel walls. Anthocyanins protect in several ways. First, they neutralize enzymes that destroy connective tissue. Second, their antioxidant capacity prevents oxidants from damaging connective tissue. Finally, they repair damaged proteins in the blood-vessel walls. Animal experiments have shown that supplementation with anthocyanins effectively prevents inflammation and subsequent blood-vessel damage.⁹

Anthocyanins’ anti-inflammatory ability has been shown to help dampen allergic reactions. In one study, Bulgarian researchers gave animals histamine and serotonin, both of which cause allergic reactions and increase capillary permeability. The animals were supplemented with a variety of flavonoids. Anthocyanins were found to have the strongest anti-inflammatory effect of any flavonoid tested.¹⁰

The Nervous System

Anthocyanins’ effects on inflammation help explain many of their protective effects elsewhere in the body. The brain is particularly vulnerable to oxidative damage. Test-tube studies show that nasunin protects lipids in animal brain tissue from oxidation.¹¹Â Peroxynitrite nitration of tyrosine residues in enzymes and proteins is believed to be a major cause of brain damage in neurodegenerative diseases and in brain trauma. Nitrated tyrosine blocks nerve growth-factor receptor sites, thus preventing new neural growth and inhibiting repair. By preventing tyrosine nitration, the anthocyanin pelargonidin may help protect against neurological diseases. Blueberry supplements have even been found to reverse age-related neurological deficits in animals.¹¹

Large Blood Vessels

Anthocyanins’ ability to counter oxidants makes them brawny atherosclerosis fighters. First, anthocyanins prevent a key step in atherogenesis: oxidation of low-density lipoproteins (LDL). Bilberry in even trace amounts effectively protects against LDL oxidation in test-tube studies. Researchers in a USDA-funded study concluded that bilberry is a “more potent” antioxidant than vitamin C or BHT, which is used as a preservative.²Â In a human study conducted in Europe, researchers found that 55 women with intrauterine growth retardation (which manifests as a decreased rate of fetal growth), who took anthocyanins, experienced decreased oxidated LDL levels from 1,104 mU/ml to 726 in two months. LDL levels rose in the control group.¹²

Second, anthocyanins protect the integrity of the endothelial cells that line blood-vessel walls. Damage to these cells stimulates white blood cell migration to the area, intitiating athlerosclerosis and stimulating red blood cell migration. A study by the USDA at Tufts University in Boston found elderberry anthocyanins are quickly taken up into endothelial cell membranes where they prevent oxidation from hydrogen peroxide and other oxidants. The researchers concluded that elderberry has “important implications on … vascular diseases.”⁵

In addition, anthocyanins relax blood vessels. In one experiment, French researchers treated animal aortas with norepinephrine, which constricts blood vessels. Presence of the anthocyanin delphinidin relaxed the aorta by 89 percent, whereas another anthocyanin, malvidin, was ineffective. The researchers concluded that delphinidin may “be involved in reduction of cardiovascular mortality related to the presence of wine, fruits, and vegetables in the diet.”¹³

Small Blood Vessels

Anthocyanins help maintain microcapillary integrity by stabilizing capillary walls. Blocked or reduced oxygen followed by reestablishment of normal supplies is called ischemia-reperfusion. Ischemia-reperfusion creates oxidants that result in white blood cell adhesion to microcapillary walls, increases capillary wall permeability, reduces blood flow, and often causes permanent capillary damage.

One of the classic experiments on anthocyanins was conducted on hamsters in Italy. Ischemia-reperfusion was created in their cheeks by a brief clamping, causing white cells to clump onto the capillary wall and damage it. After several weeks of bilberry supplementation, scientists repeated the tests. This time, normal blood supply through the capillaries was restored, fewer white blood cells stuck to the vessel walls, and permeability was significantly reduced after reperfusion.⁹

Diabetes

Microvessel damage from high blood-sugar levels causes most of the complications in diabetes. Collagen proteins become linked with sugars, resulting in abnormal polymeric blood vessel collagen. In one German study, 12 adult diabetics took 600 mg anthocyanins daily for two months. Samples of their gum tissue were taken before and after treatment. After supplementation, abnormal collagen production was significantly decreased.¹⁴ Diabetes renders capillaries more permeable to large molecules than they should be. For instance, the protein albumin migrates into the space between cells and is not adequately taken up by the lymphatic system. In a recent French study, researchers using an animal diabetic model found that those treated with bilberry maintained normal microcirculatory function including normal capillary filtration of albumin and its uptake by the lymphatic system.¹⁵

One of the most serious diabetic complications is retinopathy, which can cause blindness. Retinopathy occurs when the body attempts to repair leaking, damaged capillaries, but does so by overproducing abnormal proteins. Not only do anthocyanins prevent capillaries from leaking in the first place, but they also prevent abnormal protein proliferation. In one Italian study, 30 out of 40 people with retinopathy showed significant improvement after taking 120 mg anthocyanin daily for several weeks. None of the control subjects improved.¹⁶

Eyesight: Anthocyanins may also improve eyesight by other mechanisms. In a French study conducted in 1964, researchers vision-tested 36 people for their ability to adapt to light and dark both before and after taking bilberry anthocyanins. For several hours after supplementation, their eyesight improved significantly, although the effect wore off within 24 hours.¹⁷ A recent Japanese study found that people taking 50 mg, but not 20 mg, black currant anthocyanins adapted better to the dark and had less eye fatigue than those in the placebo group.¹⁸

 

Two recent tests on anthocyanins and vision have produced negative results. In 1999, Israeli researchers found that supplementation with 24 mg and 48 mg anthocyanins daily did not improve three measures of night vision: scotopic retinal threshold, dark adaptation rates, and mesoptic contrast sensitivity.^19 Researchers in a NASA study found that using 40 mg bilberry anthocyanins had no effect in night vision, visual acuity, or contrast sensitivity compared with placebo.²⁰

Other Effects

Anthocyanins may have other potential benefits for humans. In the laboratory, they have been found to inhibit some human tumor cells. Cyanidin and delphinidin inhibit epidermal growth factor receptor in cancer cells, while malvidin is less effective.²¹

Bilberry, traditionally used for ulcers, may increase the production of stomach mucus and protect the stomach from injury. In one uncontrolled Italian study, 10 men took 1,200 mg anthocyanins for 10 days. This increased their gastric juice secretion and mucus, while stomach acid production remained constant.²²

A recent Austrian pilot study, in conjunction with the U.S. Air Force, found a proprietary, standardized, elderberry extract reduced stress-related parameters such as blood glucose levels induced by stress.²³

Anthocyanins have received less attention than other flavonoids, despite their far-reaching effects. Because berries were such a large part of early diets, our ancestors probably ate far more anthocyanins than we do. Some researchers feel that, by comparison, we are deficient in anthocyanins. When people become aware of the antioxidant power of these compounds, perhaps we can remedy that deficiency. In the process, some of our popular foods may become even more enjoyable.

 

This is a great article. I recommend all of you to read this. Most of us do not eat grass fed beef, or raw milk… fresh vegetables and fruits…

Anthocyanin compounds are natural pigments responsible for the beautiful colors seen in fruits. These compounds possess antioxidants which are capable of fighting free radicals in the body. Studies have shown that anthocyanin compounds are rapidly absorbed. When absorbed, the compounds enter the bloodstream and go to work fighting free radicals.  Cyanidin-3-glucoside is a component of anthocyanin compounds which has shown great promise as an antioxidant to fight free radicals. Most of us do not eat fresh fruits or foods any more due to lifestyle constraints. This is why a pure extract from Medox containing these compounds are so important!

Proanthocyanins are effective antioxidants and have other activities such as inhibition of platelet activity. Several successful antioxidant products are based on proanthocyanins including grape seed extract and pine bark extract (Enzogenol and Pycnogenol). Some other fruits also contain substantial proanthocyanin concentrations such as grape, and persimmon. Additionally, the health properties of cocoa (and chocolate) are promoted due to the high proanthocyanin content. Black Currants and Bilberries contain sky-high amounts of proanthocyanins and many other anti-oxidant compounds! All of which is highly concentrated in Medox! www.medox-usa.com