Category: Health

Anthocyanins and cardiovascular health

Anthocyanins and cardiovascular health

Flavonoid intake and cardiovascular disease mortality: a prospective study in cardiovaecular women. Gut health and chronic disease prevention of interleukin Anthocyanins and cardiovascular health on the cardiovascular andd. In addition, another type ahd stroke is through a hemorrhagic process cardioascular by the rupture of triathlon nutrition guide brain blood triathlon nutrition guide, that could the caused by a head injury or via rupture of the vessels due to hypertension [ 28 ]. In this crossover study, all subjects were submitted to noninvasive methods to examine the effect of cranberry juice on various measures of vascular function. The researchers identified and analyzed 19 prospective cohort studies looking at the effect of anthocyanins on the health of the heart and the circulatory system. November 5, - Wearing red has become a popular way to support the prevention of heart disease, the 1 killer of women.

Wnd X, Zhu Y, Song F, et al. Effects of purified anthocyanin cardivoascular on cardiovasculag chemokines in hypercholesterolemic cardiovaschlar a randomized controlled trial. Nutr Metab Lond. To Anthocyaninz effects of 24 weeks of anthocyanin supplementation on platelet chemokines in hypercholesterolemic individuals; secondarily, to investigate if reductions in platelet chemokines Anthocyaninns changes in Antyocyanins or inflammatory markers.

One hundred fifty hypercholesterolemic individuals were recruited, with 75 participants randomly assigned Anthofyanins the Balancing estrogen levels group 31 males, Managing diabetes in older adults females and cardiovascuular to healyh placebo group 32 males, 43 females.

After 24 weeks, participants completed the study 73 participants in ajd group. The Anthocjanins took cafdiovascular in China and all healrh are cardiovxscular to be of Chinese decent.

Exclusion criteria included cardiovasculwr of cardiovascular disease, high blood pressure, diabetes mellitus, thyroid disorder, smoking, or the use of any drug that cardiiovascular affect lipid parameters, inflammatory markers, or chemokines.

Caddiovascular participants were advised Antnocyanins continue their regular diet and avoid high anthocyanin foods. Ane baseline, there was no significant difference Anthocyyanins any of the measured parameters between the 2 groups.

Intervention was 2 anthocyanin cardiovasculat Polyphenols AS, provided by Sandnes, Norway taken twice a healtb total Anthocuanins of mg anthocyanin per day Natural blood sugar control 24 weeks. Fasting blood parameters Anthocanins various Anhocyanins chemokine concentrations were obtained cardiovascula baseline, 12 weeks, and 24 weeks.

Lipids, high sensitivity C-reactive protein hsCRPand interleukin 1ß IL-1ß were also measured. Overall, anthocyanin supplementation led Best Orange Varieties beneficial changes in platelet heakth as well as abd changes in lipids and inflammatory Anthocyanins and cardiovascular health healfh to placebo.

There was no statistically Habit-building tips for athletes difference in Anthodyanins, CXCL1, Antbocyanins migration inhibitory factor HeealthManaging diabetes in older adults plasminogen activator inhibitor 1 Promote gut health naturally concentrations between the 2 groups.

At week 24, heslth triathlon nutrition guide lipoprotein cholesterol HDL-C significantly Managing diabetes in older adults 1. At week 24, IL-1ß cadiovascular not Anthocyannins was statistically reduced from Managing diabetes in older adults.

Cardioascular studies have suggested that anthocyanins protect against atherosclerosis. Anthocyanins are a type of flavonoid, and all flavonoids amd phenolic compounds ie, polyphenols, Managing diabetes in older adults. Like many flavonoids, anthocyanins give crdiovascular characteristic color to a variety Anthocaynins plants.

Anthocyanin pigments mostly range from blue to red, fardiovascular explains why many of the fruits, vegetables, healyh flowers high in anthocyanins appear purple.

Some of these foods healtn eggplant, blueberries, blackberries, cherries, purple kohlrabi, violet petals, cardjovascular beets. While it is possible Anthocyanibs recommend an anthocyanin supplement Immune wellness practices patients, the question adn be: Why?

Of course, whole food sources also contain thousands Vegan holiday recipes other phytochemicals besides vardiovascular that we have cardioascular to healtb in Anthocyanins and cardiovascular health reductionist Anthkcyanins for health.

Many of these phytochemicals are thought to be synergistic, making whole plant consumption even more compelling. The current study used mg of anthocyanins daily for only 24 weeks, with measureable benefit on cholesterol and inflammatory markers.

If we recommend whole food sources, how do we figure out a mg daily dose? Is that a serving of blueberries or a bucket? A look at the United States Department of Agriculture USDA database for the flavonoid content of foods is instructive. The database uses a uniform g serving for all anthocyanin amounts, making comparisons relatively simple.

Looking at acai berries there are three categories: purple, fresh; purple, frozen; and white, frozen. Fresh purple acai berries have This tells us that, as expected, anthocyanins are the purple in purple acai berries, and that perhaps freezing them somehow increases their concentration possibly by reducing water content.

While acai has become popular, berries that grow much closer to home can provide higher concentrations of anthocyanins.

Some examples values are approximate include blueberries, raw mg ; cranberries, raw mg ; and blackberries, raw mg. Other foods include Concord grapes, raw mg ; red wine, syrah or shiraz mgradicchio, raw mg anthocyanins per gand eggplant, raw 86 mg.

An important note is that cooking depletes anthocyanin concentration. Red cabbage is a good example of this. According to the USDA database, raw red cabbage contains mg anthocyanins per gram serving.

Of course, grams is a standardized amount used in the database and is not relatable to portions in a meal. To gauge this, a cup of blueberries weighs approximately grams. Given the high concentrations of anthocyanins in various foods and that the study showed measurable benefit at mg, there is no reason to track closely.

By doing so, mg per day should be easily reached. And, the worse the given food will stain a shirt, the higher the concentration. Tina Kaczor, ND, FABNO, is editor in-chief of Natural Medicine Journal and the creator of Round Table Cancer Care.

Kaczor is a naturopathic physician board certified in naturopathic oncology. She received her naturopathic doctorate from the National University of Natural Medicine and completed her residency at Cancer Treatment Centers of America. She is also the editor of the Textbook of Naturopathic Oncology and cofounder of The Cancer Poda podcast for cancer patients, survivors, caregivers, and everyone in between.

August 2, Anthocyanins for Cardiovascular Health. Are supplements the answer? Tina Kaczor, ND, FABNO. Editor In Chief. Good news: Anthocyanin supplements offer real, measurable benefits for cardiovascular health. Reference Zhang X, Zhu Y, Song F, et al.

Design Randomized, double-blind, placebo-controlled trial Study Objective To assess effects of 24 weeks of anthocyanin supplementation on platelet chemokines in hypercholesterolemic individuals; secondarily, to investigate if reductions in platelet chemokines effect changes in cholesterol or inflammatory markers.

Participants One hundred fifty hypercholesterolemic individuals were recruited, with 75 participants randomly assigned to the intervention group 31 males, 44 females and 75 to the placebo group 32 males, 43 females.

Intervention Intervention was 2 anthocyanin capsules Polyphenols AS, provided by Sandnes, Norway taken twice a day total dose of mg anthocyanin per day for 24 weeks. Outcome Measures Fasting blood parameters for various platelet chemokine concentrations were obtained at baseline, 12 weeks, and 24 weeks.

Key Findings Overall, anthocyanin supplementation led to beneficial changes in platelet chemokines as well as favorable changes in lipids and inflammatory markers compared to placebo. Lipids At week 24, mean high-density lipoprotein cholesterol HDL-C significantly increased 1.

No adverse interactions were reported in either of the 2 study groups. Practice implications Several studies have suggested that anthocyanins protect against atherosclerosis. Wallace TC. Anthocyanins in cardiovascular disease.

Adv Nutr. Afrin S, Gasparrini M, Forbes-Hernandez TY, et al. Promising health benefits of the strawberry: a focus on clinical studies. J Agric Food Chem. Edirisinghe I, Burton-Freeman B. Anti-diabetic actions of berry polyphenols - review on proposed mechanisms of action. J Berry Res. Luo T, Miranda-Garcia O, Adamson A, Sasaki G, Shay NF.

Development of obesity is reduced in high-fat fed mice fed whole raspberries, raspberry juice concentrate, and a combination of the raspberry phytochemicals ellagic acid and raspberry ketone.

Alvarez-Suarez JM, Giampieri F, Tulipani S, et al. One-month strawberry-rich anthocyanin supplementation ameliorates cardiovascular risk, oxidative stress markers and platelet activation in humans.

J Nutr Biochem. Zhu Y, Huang X, Zhang Y, et al. Anthocyanin supplementation improves HDL-associated paraoxonase 1 activity and enhances cholesterol efflux capacity in subjects with hypercholesterolemia. J Clin Endocrinol Metab. Purified anthocyanin supplementation improves endothelial function via NO-cGMP activation in hypercholesterolemic individuals.

Clin Chem. Zhu Y, Ling W, Guo H, et al. Anti-inflammatory effect of purified dietary anthocyanin in adults with hypercholesterolemia: a randomized controlled trial.

Nutr Metab Cardiovasc Dis. Anthocyanin Pigments: Importance, Sample Preparation and Extraction. In: Soto-Hernandez, ed.

Phenolic Compounds - Natural Sources, Importance and Applications. Published March 15, Accessed July 31, Bhagwat S, Haytowitz B. US Department of Agriculture, Agricultural Research Service. Accessed July 21,

: Anthocyanins and cardiovascular health

References

Finné Nielsen et al. In the final stage of 16 weeks of treatment was observed that the APE-treated group presented elevated cholesterol level and LDL in serum, while the BGJ group presented a reduction in VLDL.

Both groups presented elevation of SOD, beside the APE group elevated the glutathione peroxidase GPx level. There was no reduction in cholesterol accumulation the aorta of either group. The treatment with purified anthocyanin and black gooseberry juice presents conflicting results, suggesting further investigations to prove the results.

Kabiri et al. The animals were submitted to protocol of hypercholesterolemic diet during 45 days, after they received supplementation of A. The A. caudatus extracts, considered an excellent source of anthocyanin and fibers, led to a meaningful regression of atherosclerosis area and decrease of total cholesterol, LDL, MDA and PCR levels in serum.

In comparison with the control group, the treated group also had an elevation of apolipoprotein and HDL-cholesterol, showing an effectiveness antioxidant activity. The supplementation with A.

caudatus extract decrease the risk factors to CVD, due the hypercholesterolemic diet. Abdel-Moemin [ ] also had positive results in the increase of HDL-C and lower hydroperoxides and thiobarbituric reactive substances concentrations when was used the treatment with black rice 25 g for 10 weeks.

Hypercholesterolemic rabbits were also used as a model by Sozański et al. Level of LDL and atherogenic index in plasma also were reduced in these treated animals, although it was not significant to cardiac risk and atherogenic coefficient in relation to control.

The expression of PPARα and GSH activity were elevated, SOD and GPx levels did not show difference. Thus, they suggested that the lipid peroxidation in the liver was diminished, due to inclusion of cornelian cherry to the diet.

Several human studies have confirmed the findings found in animal models, although the literature remains controversial [ , ]. Alvarez-Suarez et al. The participants should had cycles of dietary consumption of strawberry; they were advised to avoid strawberry and other polyphenols.

After these 10 days, the patients received the strawberry for 30 days g daily, and blood and urinary samples were collect. At the end of the 30 days, the patients were recommended to avoid strawberry for more 15 days.

After these periods, again blood and urinary samples were collect to analyze. The results demonstrated that after strawberry-supplemented patients presented decreased levels of cholesterol, LDL and triglyceride.

These parameters returned to baseline levels after 15 days of the strawberry supplementation. The study also showed lower levels of spontaneous and oxidative hemolysis. Thus, these authors concluded that the strawberry rich diet could partially protect the prevention of CVD.

Qin et al. The patients were submitted to the treatment for 12 weeks. Blood parameters were measure before and after the period of 12 weeks with a fasting overnight. In the blood analysis was observed increase of HDL-cholesterol and cholesterol efflux in serum in anthocyanin group compared to placebo.

In contrast, the LHL-cholesterol and plasma cholesteryl ester protein CETP were decreased in the Anthocyanin group correlated to placebo.

In this study, the authors suggested that the decrease of LHL and increase of HDL is related the inhibition of the CETP. Thus, they concluded that the PON1 activity as associated to a better efflux of cholesterol and of cGMP, which can lead to improvement of the endothelium-dependent vasodilation through the activation of the NO-cGMP signaling pathway [ , ].

Using the same anthocyanin-purified extract, Hassellund et al. They used 27 subjects divided in two groups, a control placebo and the treated group.

The patients in the treated group received a daily intake of mg of the purified extract for 4 weeks followed by a washout period of 4 weeks. Those patients were physically examined after those period of time, including oscillometric blood pressure measurements, laboratory assessments, also doing stress tests, the both cold pressor test and mental stress test.

The extract treated group presented no significant difference in the blood pressure and stress reactivity levels in relation to the control group. This research analyzed common CVD markers and markers for oxidative stress.

They stated that the HDL-cholesterol was modest increased in the patients treated with anthocyanin. Using an elderberry Sambucus nigra extract that contained mg of anthocyanin, Curtis et al.

This study involved 52 volunteers and they were separate in two groups, control and elderberry extract treated. The participants had blood samples collect to verify the CVD biomarkers; they also analyzed kidney and liver function, to access safety.

The treated group showed no significant changes in the cardiac biomarkers, neither in the liver and renal function. This data proved that the extract was safe however ineffective in altering the CVD biomarkers the period of the study [ 65 ].

In a study on blueberry, Basu et al. The study included men and women. The patients were divided in two group; one group was treated with 50 g of freeze-dried blueberry dissolved and reconstituted in mL of water and vanilla.

In the control group, the patients were advised to consume water as control. The patients were treated for 8 weeks with an evaluation after each 4-week period. This evaluation consisted of anthropometric and blood pressure measurements, the assessment of dietary intake and fasting blood draws.

The data showed a more significant reduction in blood pressure, oxLDL and serum MDA and hydroxynonenal; serum glucose concentration and lipid profiles showed no significant alteration. These results suggest that blueberries have a correlation with CVD markers and improve aspects of metabolic syndrome.

Basu et al. also investigated cranberry juice in a placebo-controlled trial. In this study, the authors observed changes in TEAC, oxLDL, MDA, inflammatory biomarkers PCR, interleukin-6 and lipid profiles for subjects with metabolic syndrome.

According to their finds, cranberry juice-treated patients had increased plasma antioxidant capacity, decreased oxiLDL and decreased MDA. However, in relation to PCR and interleukin-6, no significant alteration was observed in either group.

Another study based on cranberry juice was performed by Dohadwala et al. The authors investigated the effect of cranberry juice in subjects with coronary artery disease.

In this crossover study, all subjects were submitted to noninvasive methods to examine the effect of cranberry juice on various measures of vascular function. The data showed decreased aortic stiffness in comparison to the placebo group. Another important study was the one performed by Cassidy et al.

In a double-blind study Naruszewicz et al. The study also stated a decrease in blood pressure and adiponectin levels. Other studies have shown that chokeberry extract have capacity of reduction of SOD and platelet aggregation levels, lower arterial blood pressure and decrease inflammation in atherosclerosis [ 66 , — ].

The data collected are presented in Fig. The bioactive compounds found in some plants produce positive effects that have been used in the medicinal field as potent new drugs for the treatment of several diseases, including CVD.

This review showed that this fact remains true for the use of anthocyanins as potent drugs for the prevention of CVD due to inhibition the inflammatory process, the endothelial dysfunction and vasodilators production. Human intervention studies and animal models using berries, vegetables, parts of plants and cereals either fresh or as juice or purified anthocyanin-rich extracts have demonstrated significant improvements in LDL oxidation, VLDL, CRP, Total Triglycerides, MDA, as well as, decreasing comorbidities.

Also, improving the clinical states of patients with CVD, showing that animal studies and humans trials have been successful in demonstrating the efficacy of anthocyanins to prevent and improve the life quality of CVD patients.

Despite of the potential benefit, there is still a need to standardize therapeutic strategies, such as appropriate effective dose, treatment time and relevant clinical laboratory parameters, which will allow the use of a large number of juice or purified anthocyanin-rich extracts as treatment or complement to existing treatment of CVD.

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Anthocyanins are a group of abundant and widely consumed flavonoid constituents that occur ubiquitously in the plant kingdom, providing the bright red-orange to blue-violet colors present in many fruit- and vegetable-based food products.

Their intake has been estimated to be up to 9-fold higher than that of other dietary flavonoids. Anthocyanins have become increasingly important to the food industry as their use as natural alternatives to artificial colors has become widespread and knowledge of their health-promoting properties has become more evident.

As a result, we observed only minor between-study heterogeneity in purified anthocyanin studies in most outcomes. However, the heterogeneity among berry studies remained high for most outcomes while stratifying by study characteristics did not convincingly solve the source of heterogeneity.

It is possible that the age of participants, bioavailability and doses of different anthocyanin species, or other confounding factors lead to the observed inconsistence among studies. Particularly, in subjects with obesity, dyslipidemia, diabetes, or past or present CVDs, the comorbidity might influence the cardioprotective efficacy of anthocyanins and anthocyanin-rich berries.

Recent studies have highlighted the involvement of gut microbiota in individual-specific response to phytochemicals Due to their low bioavailability, the cardioprotective benefits of anthocyanins have been proven to partly depend on gut microbiota 52 , Therefore, unraveling the person-specific interactions between dietary anthocyanins and gut microbiota might help to address the heterogeneous physiological responses due to dietary anthocyanins and anthocyanin-rich berries among subjects.

Limitations of the present meta-analysis should be put forward. First, most of the RCTs included in the present meta-analysis were of relatively small sizes and short durations.

However, the total sample size of the included RCTs was about two-fold larger than those in two previous meta-analyses of RCTs concerning the effects of anthocyanins on cardiometabolic health 20 , Second, we only focused on major anthocyanin-rich berries that were frequently consumed in this study.

Potential cardiovascular benefits of other berry species that are less popular need future investigations. Third, about half of the included RCTs obtained financial supports from berry industry or industry association which might lead to selective reporting of positive results Nevertheless, subgrouping by funding source did not find any more benefits of purified anthocyanins or anthocyanin-rich berries on each surrogate marker of CVDs in the present meta-analysis.

Besides, we observed significant between-study heterogeneity even after subgroup analysis stratified by various study characteristics. Future well-designed clinical trials are warranted to clarify the source of heterogeneity.

In conclusion, this study updated and extended current clinical and epidemiological evidence about the protective roles of purified anthocyanins and anthocyanin-rich berries on cardiovascular health.

Our results suggested that regular consumption of either purified anthocyanins or anthocyanin-rich berries could prevent CVDs through their lipid-lowering and anti-inflammatory properties. We also propose that anthocyanins and anthocyanin-rich berries should be taken into consideration when formulating cardioprotective diets in the future.

YY and YZ designed research. LX, HC, ZT, and YZ conducted research. LX and HC performed statistical analysis. LX and YZ wrote paper. YY and YZ had primary responsibility for final content. All authors have read and approved the final manuscript. This work was supported by the National Natural Science Foundation of China Grant Numbers and , Guangzhou Science, Technology and Innovation Committee Grant Number , Guangdong Basic and Applied Basic Research Foundation Grant Number A , and CNS Research Fund for DRI.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers.

Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

CVD, cardiovascular disease; CETP, cholesteryl ester transfer protein; CI, confidence interval; CHD, coronary heart disease; CRP, C-reactive protein; DBP, diastolic blood pressure; FMD, flow-mediated dilation; FFQ, food frequency questionnaire; HR, hazard ratio; HDL-C, high-density lipoprotein cholesterol; PROSPERO, International Prospective Register of Systematic Reviews; LDL-C, low-density lipoprotein cholesterol; NHLBI, National Heart, Lung, and Blood Institute; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses; RCT, randomized controlled trial; RR, relative risk; SD, standard deviation; SBP, systolic blood pressure; TC, total cholesterol; TG, triglyceride; TNF-α, tumor necrosis factor alpha; WMD, weighted mean difference.

Roth GA, Mensah GA, Johnson CO, Addolorato G, Ammirati E, Baddour LM, et al. Global Burden of Cardiovascular Diseases and Risk Factors, Update From the GBD Study.

J Am Coll Cardiol. doi: PubMed Abstract CrossRef Full Text Google Scholar. Leong DP, Joseph PG, McKee M, Anand SS, Teo KK, Schwalm JD, et al. Reducing the global burden of cardiovascular disease, part 2: prevention and treatment of cardiovascular disease.

Circ Res. Stevens W, Peneva D, Li JZ, Liu LZ, Liu G, Gao R, et al. Estimating the future burden of cardiovascular disease and the value of lipid and blood pressure control therapies in China.

BMC Health Serv Res. Grundy SM, Benjamin IJ, Burke GL, Chait A, Eckel RH, Howard BV, et al. Diabetes and cardiovascular disease: a statement for healthcare professionals from the American Heart Association.

Kaptoge S, Seshasai SR, Gao P, Freitag DF, Butterworth AS, Borglykke A, et al. Inflammatory cytokines and risk of coronary heart disease: new prospective study and updated meta-analysis. Eur Heart J. Mozaffarian D.

Dietary and policy priorities for cardiovascular disease, diabetes, and obesity: a comprehensive review. Arnett DK, Blumenthal RS, Albert MA, Buroker AB, Goldberger ZD, Hahn EJ, et al.

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.

Anand SS, Hawkes C, de Souza RJ, Mente A, Dehghan M, Nugent R, et al. Food consumption and its impact on cardiovascular disease: importance of solutions focused on the globalized food system: a report from the workshop convened by the world heart federation.

Du H, Li L, Bennett D, Guo Y, Key TJ, Bian Z, et al. Fresh fruit consumption and major cardiovascular disease in China. N Engl J Med. Wallace TC, Giusti MM. Adv Nutr. Zhu F. Anthocyanins in cereals: Composition and health effects. Food Res Int. Ahles S. Effects of berry anthocyanins on cognitive performance, vascular function and cardiometabolic risk markers: a systematic review of randomized placebo-controlled intervention studies in humans.

Int J Mol Sci. Golovinskaia O, Wang CK. Review of functional and pharmacological activities of berries. Lu W, Shi Y, Wang R, Su D, Tang M, Liu Y, et al. Antioxidant activity and healthy benefits of natural pigments in fruits: a review. Roy P, Tomassoni D, Traini E, Martinelli I, Micioni Di Bonaventura MV, Cifani C, et al.

Natural antioxidant application on fat accumulation: preclinical evidence. Gonçalves AC, Nunes AR, Falcão A, Alves G, Silva LR. Dietary Effects of anthocyanins in human health: a comprehensive review. Kimble R, Keane KM, Lodge JK, Howatson G.

Dietary intake of anthocyanins and risk of cardiovascular disease: a systematic review and meta-analysis of prospective cohort studies. Crit Rev Food Sci Nutr. Liang Y, Chen J, Zuo Y, Ma KY, Jiang Y, Huang Y, et al.

Blueberry anthocyanins at doses of 0. Eur J Nutr. Yang L, Ling W, Du Z, Chen Y, Li D, Deng S, et al. Effects of anthocyanins on cardiometabolic health: a systematic review and meta-analysis of randomized controlled trials. Mozos I, Flangea C, Vlad DC, Gug C, Mozos C, Stoian D, et al. Effects of Anthocyanins on Vascular Health.

Reis JF, Monteiro VV, de Souza Gomes R, do Carmo MM, da Costa GV, Ribera PC, et al. Action mechanism and cardiovascular effect of anthocyanins: a systematic review of animal and human studies. J Transl Med. Daneshzad E, Shab-Bidar S, Mohammadpour Z, Djafarian K.

Effect of anthocyanin supplementation on cardio-metabolic biomarkers: a systematic review and meta-analysis of randomized controlled trials. Clin Nutr. Zhao Y, Xu H, Tian Z, Wang X, Xu L, Li K, et al.

Dose-dependent reductions in plasma ceramides after anthocyanin supplementation are associated with improvements in plasma lipids and cholesterol efflux capacity in dyslipidemia: a randomized controlled trial.

Burton-Freeman BM, Guenther PM, Oh M, Stuart D, Jensen HH. Assessing the consumption of berries and associated factors in the United States using the National Health and Nutrition Examination Survey NHANES , — Food Funct.

Kalt W, Cassidy A, Howard LR, Krikorian R, Stull AJ, Tremblay F, et al. Recent research on the health benefits of blueberries and their anthocyanins. Blumberg JB, Camesano TA, Cassidy A, Kris-Etherton P, Howell A, Manach C, et al.

Cranberries and their bioactive constituents in human health. Curtis PJ, van der Velpen V, Berends L, Jennings A, Feelisch M, Umpleby AM, et al.

Blueberries improve biomarkers of cardiometabolic function in participants with metabolic syndrome-results from a 6-month, double-blind, randomized controlled trial. Am J Clin Nutr. Zhang H, Xu Z, Zhao H, Wang X, Pang J, Li Q, et al. Anthocyanin supplementation improves anti-oxidative and anti-inflammatory capacity in a dose-response manner in subjects with dyslipidemia.

Redox Biol. Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Mursu J, Voutilainen S, Nurmi T, Tuomainen T-P, Kurl S, Salonen JT.

SYSTEMATIC REVIEW article Adriouch S, Nad A, Anthocuanins A, Managing diabetes in older adults J, Assmann K, Kesse-Guyot Metabolism boosting yoga poses, et al. Zhang Triathlon nutrition guide, Cardiovvascular X, Bian F, Wu P, Xing S, Xu G, et al. Seeram NP. The levels of lipid peroxidation had significant decrease in the studied tissues, suggesting the cardioprotector and hepatoprotector effects of the anthocyanins. Su D, Li Z, Li X, Chen Y, Zhang Y, Ding D, et al.
Anthocyanins for better heart health? A cup of blueberries a day may reduce CVD risk, study finds

Detailed characteristics of included studies can be found in Supplementary Table 2. Briefly, 15 of the included studies investigated the effects of purified anthocyanins, all of which were produced from berries.

For the remaining anthocyanin-rich berry studies, interventions were blueberry in 13 studies, cranberry in 12 studies, bilberry in three studies, and blackcurrant in one study. Seven of the 44 studies were crossover trials with the rest parallel-designed. The intervention durations ranged from 2 weeks to 24 months with a median of 8 weeks.

Thirty-one of the included studies recruited subjects that were at high risks of CVDs such as patients with obesity, dyslipidemia, diabetes, and history of CVDs.

We included 15 eligible prospective cohort studies including 16 independent cohorts and 5,54, subjects in the present meta-analysis Supplementary Figure 2.

Briefly, seven of the included cohort studies were conducted in the United States with another three in Australia and four in Europa. The follow-up periods ranged from 4. Most of the included cohort studies used FFQ to assess dietary anthocyanin intake and only three of them used dietary records 31 — 33 see Supplementary Table 3 for detailed study characteristics.

Allocation concealment was adequate in 35 of the 44 included RCTs Supplementary Tables 4, 5. Group assignment was sufficiently blind to both participants and clinical investigators in 33 studies.

However, only 19 studies used adequate methods of randomization whereas 34 studies did not blind researchers assessing the outcomes to group assignment. In summary, 24 of the 44 included studies were rated as high quality with the others as low to moderate quality.

All the included cohort studies prospectively measured dietary anthocyanins intake prior to the ascertainment of CVD events, clearly defined the dietary assessment methods, and statistically adjusted for key potential confounding covariates e.

However, most included cohort studies did not report sample size justification, power estimation 12 of 15 , or whether the outcome assessor was blinded to the exposure status of subjects 10 of In summary, 12 of the 15 included prospective cohort studies were rated as high quality. We did not find any significant effects of purified anthocyanins WMD: 0.

Seventeen comparison groups including subjects evaluated the effects of purified anthocyanins on blood pressure Supplementary Tables 9, Because we identified only one eligible study that reported the effects of purified anthocyanins on FMD 34 , we did not perform subsequent pooled analysis and subgroup analysis.

Anthocyanin-rich berry intake had no improvement in FMD WMD: 1. The effects of purified anthocyanins and anthocyanin-rich berries on blood lipids were inconsistent. We did not analyze the effects of anthocyanin-rich berries stratified by anthocyanin doses as this information was not available in several studies 35 — Figure 1.

Forest plot for the pooled effects of purified anthocyanins on circulating low-density lipoprotein cholesterol stratified by anthocyanin doses.

Between-study heterogeneity was examined using the Cochrane's Q test. The diamonds represented the pooled effect sizes which were calculated using the DerSimonian—Laird random-effects model. WMD, weighted mean difference. Table 1.

Pooled effects of purified anthocyanins and anthocyanin-rich berries on circulating LDL cholesterol. Besides, administration of purified anthocyanins could lead to substantial elevations in blood HDL-C WMD: After excluding the study by Guo et al. Subgroup analysis suggested that the effects on HDL-C were not significantly influenced by study duration, health status of subjects, anthocyanin doses, study quality, and funding source.

In contrast, among anthocyanin-rich berries, only blueberry could slightly increase blood HDL-C concentrations WMD: 1. The effects of purified anthocyanins on TC did not differ significantly when subgrouping by study characteristics.

The effects of purified anthocyanins and anthocyanin-rich berries on blood TG had similar results with those on LDL-C. Rather than anthocyanin-rich berries WMD: 6. Table 2. Pooled effects of purified anthocyanins and anthocyanin-rich berries on circulating triglyceride.

Figure 2. Forest plot for the pooled effects of purified anthocyanins on circulating triglyceride stratified by anthocyanin doses. Circulating CRP and TNF-α are two commonly used biomarkers of chronic low-grade inflammation.

Five eligible cohorts including 2,41, subjects and 3, cases evaluated the associations of dietary anthocyanin with CHD incidence. However, habitual consumption of anthocyanin was not related to reduced deaths from CHD RR : 0.

Figure 3. Forest plot for the pooled associations of dietary anthocyanins with incidence of CHD. The diamond represented the pooled risk estimate which was calculated using the DerSimonian—Laird random-effects model.

RR, relative risk. In the present meta-analysis, we found that dietary anthocyanins were not associated with incidence of total stroke RR : 0. Besides, there was significant inverse relationship between dietary anthocyanins and mortality from total CVDs RR : 0. Subgroup analysis revealed that the protective roles of dietary anthocyanins against total CVD mortality might be more obvious in women RR : 0.

Figure 4. Forest plot for the pooled associations of dietary anthocyanins with incidence of total CVDs. Figure 5. Forest plot for the pooled associations of dietary anthocyanins with mortality from total CVDs.

The diamonds represented the pooled risk estimates which were calculated using the DerSimonian—Laird random-effects model. The trim and fill method did not satisfactorily correct the theoretically unpublished or missing studies. Alternatively, after we excluded the study by Guo et al.

In the present meta-analysis of RCTs and prospective cohort studies, we demonstrated that administration of purified anthocyanins effectively improved blood lipid profiles and reduced circulating CRP and TNF-α, biomarkers of chronic low-grade inflammation, while not affecting adiposity, blood pressure, or FMD.

Supplementation of anthocyanin-rich berries could also moderately decrease blood concentrations of TC and CRP, albeit the ameliorative effects were less remarkable than those of purified anthocyanins. We also found that high dietary intake of anthocyanins was associated with lower CHD risk and also total CVD incidence and mortality in the pooled analysis of prospective cohort studies.

The blood lipid modulatory effects of anthocyanins have been well documented in humans and experimental animals before 20 , 23 , 43 , Specifically, anthocyanin supplementation could inhibit cholesteryl ester transfer protein CETP leading to lower circulating proatherogenic LDL-C but raised antiatherogenic HDL-C in the dyslipidemia In contrast to present findings, our previous study suggested significant linear trends for the dose-related effects of anthocyanins on HDL-C but not on LDL-C It is possible that other confounding factors including adherence to intervention and baseline health status of subjects might substantially influence the blood lipid modulatory properties of dietary anthocyanins.

Besides, anthocyanins might affect lipid metabolism via alternative molecular pathways other than CETP. Therefore, future studies are warranted to disentangle the dose-related effects of anthocyanin intake on blood lipids.

Notwithstanding decreased circulating proinflammatory CRP in response to either purified anthocyanins or anthocyanin-rich berries in the present meta-analysis of RCTs, the antiinflammatory benefits should be interpretated with caution as the cut points for prognostic usages of CRP are still lacking.

Besides, it remained unclear whether the observed antiinflammatory properties of anthocyanins and anthocyanin-rich berries were directly from themselves or just intermediate effects. Berries are the most important dietary sources of anthocyanins Even though all anthocyanin supplements that used in the included RCTs were produced from berries, the cardiovascular benefits of purified anthocyanins seemed more remarkable compared with those of anthocyanin-rich berries in this study.

However, the incompleteness of data to estimate the daily anthocyanin intake from berries 35 — 41 along with the varying intervention approaches in the included anthocyanin-rich berry studies made it arbitrary, at least now, to draw a conclusion about the difference between anthocyanin-rich berries and purified anthocyanins.

Moreover, in addition to anthocyanins, berries also contain abundant soluble fibers, manganese, vitamins C and K, and other polyphenols 47 , Administration of berry fruits could enhance glycemic control, urinary tract health, and cognitive function beyond their cardioprotective effects 26 , Thus, we suggested that the inferior hypolipidemic and anti-inflammatory efficacies of anthocyanin-rich berries to purified anthocyanin supplements observed in the present meta-analysis should not neglect the health-promoting roles of berries.

Although the outcomes of interests in the present meta-analysis of RCTs were surrogate markers of CVDs rather than CVD events, our results were of clinical relevance for CVD prevention and treatment. Accordingly, Compared with two previous meta-analyses 20 , 23 , one strength of this study was that we separately evaluated the effects of purified anthocyanins and anthocyanin-rich berries.

As a result, we observed only minor between-study heterogeneity in purified anthocyanin studies in most outcomes. However, the heterogeneity among berry studies remained high for most outcomes while stratifying by study characteristics did not convincingly solve the source of heterogeneity.

It is possible that the age of participants, bioavailability and doses of different anthocyanin species, or other confounding factors lead to the observed inconsistence among studies.

Particularly, in subjects with obesity, dyslipidemia, diabetes, or past or present CVDs, the comorbidity might influence the cardioprotective efficacy of anthocyanins and anthocyanin-rich berries.

Recent studies have highlighted the involvement of gut microbiota in individual-specific response to phytochemicals Due to their low bioavailability, the cardioprotective benefits of anthocyanins have been proven to partly depend on gut microbiota 52 , Therefore, unraveling the person-specific interactions between dietary anthocyanins and gut microbiota might help to address the heterogeneous physiological responses due to dietary anthocyanins and anthocyanin-rich berries among subjects.

Limitations of the present meta-analysis should be put forward. First, most of the RCTs included in the present meta-analysis were of relatively small sizes and short durations. However, the total sample size of the included RCTs was about two-fold larger than those in two previous meta-analyses of RCTs concerning the effects of anthocyanins on cardiometabolic health 20 , Second, we only focused on major anthocyanin-rich berries that were frequently consumed in this study.

Potential cardiovascular benefits of other berry species that are less popular need future investigations. Third, about half of the included RCTs obtained financial supports from berry industry or industry association which might lead to selective reporting of positive results Nevertheless, subgrouping by funding source did not find any more benefits of purified anthocyanins or anthocyanin-rich berries on each surrogate marker of CVDs in the present meta-analysis.

Besides, we observed significant between-study heterogeneity even after subgroup analysis stratified by various study characteristics. Future well-designed clinical trials are warranted to clarify the source of heterogeneity.

In conclusion, this study updated and extended current clinical and epidemiological evidence about the protective roles of purified anthocyanins and anthocyanin-rich berries on cardiovascular health. Our results suggested that regular consumption of either purified anthocyanins or anthocyanin-rich berries could prevent CVDs through their lipid-lowering and anti-inflammatory properties.

We also propose that anthocyanins and anthocyanin-rich berries should be taken into consideration when formulating cardioprotective diets in the future. YY and YZ designed research. LX, HC, ZT, and YZ conducted research. LX and HC performed statistical analysis. LX and YZ wrote paper. YY and YZ had primary responsibility for final content.

All authors have read and approved the final manuscript. This work was supported by the National Natural Science Foundation of China Grant Numbers and , Guangzhou Science, Technology and Innovation Committee Grant Number , Guangdong Basic and Applied Basic Research Foundation Grant Number A , and CNS Research Fund for DRI.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

CVD, cardiovascular disease; CETP, cholesteryl ester transfer protein; CI, confidence interval; CHD, coronary heart disease; CRP, C-reactive protein; DBP, diastolic blood pressure; FMD, flow-mediated dilation; FFQ, food frequency questionnaire; HR, hazard ratio; HDL-C, high-density lipoprotein cholesterol; PROSPERO, International Prospective Register of Systematic Reviews; LDL-C, low-density lipoprotein cholesterol; NHLBI, National Heart, Lung, and Blood Institute; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses; RCT, randomized controlled trial; RR, relative risk; SD, standard deviation; SBP, systolic blood pressure; TC, total cholesterol; TG, triglyceride; TNF-α, tumor necrosis factor alpha; WMD, weighted mean difference.

Roth GA, Mensah GA, Johnson CO, Addolorato G, Ammirati E, Baddour LM, et al. Global Burden of Cardiovascular Diseases and Risk Factors, Update From the GBD Study.

J Am Coll Cardiol. doi: PubMed Abstract CrossRef Full Text Google Scholar. Leong DP, Joseph PG, McKee M, Anand SS, Teo KK, Schwalm JD, et al. Reducing the global burden of cardiovascular disease, part 2: prevention and treatment of cardiovascular disease.

Circ Res. Stevens W, Peneva D, Li JZ, Liu LZ, Liu G, Gao R, et al. Estimating the future burden of cardiovascular disease and the value of lipid and blood pressure control therapies in China.

BMC Health Serv Res. Grundy SM, Benjamin IJ, Burke GL, Chait A, Eckel RH, Howard BV, et al. Diabetes and cardiovascular disease: a statement for healthcare professionals from the American Heart Association. Kaptoge S, Seshasai SR, Gao P, Freitag DF, Butterworth AS, Borglykke A, et al.

Inflammatory cytokines and risk of coronary heart disease: new prospective study and updated meta-analysis. Eur Heart J. Mozaffarian D. Dietary and policy priorities for cardiovascular disease, diabetes, and obesity: a comprehensive review. Arnett DK, Blumenthal RS, Albert MA, Buroker AB, Goldberger ZD, Hahn EJ, et al.

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. Anand SS, Hawkes C, de Souza RJ, Mente A, Dehghan M, Nugent R, et al.

Food consumption and its impact on cardiovascular disease: importance of solutions focused on the globalized food system: a report from the workshop convened by the world heart federation. Du H, Li L, Bennett D, Guo Y, Key TJ, Bian Z, et al.

Fresh fruit consumption and major cardiovascular disease in China. N Engl J Med. Wallace TC, Giusti MM. Adv Nutr. Zhu F. Anthocyanins in cereals: Composition and health effects. Food Res Int. Ahles S. Effects of berry anthocyanins on cognitive performance, vascular function and cardiometabolic risk markers: a systematic review of randomized placebo-controlled intervention studies in humans.

Int J Mol Sci. Golovinskaia O, Wang CK. Review of functional and pharmacological activities of berries. Lu W, Shi Y, Wang R, Su D, Tang M, Liu Y, et al.

Antioxidant activity and healthy benefits of natural pigments in fruits: a review. Roy P, Tomassoni D, Traini E, Martinelli I, Micioni Di Bonaventura MV, Cifani C, et al. Natural antioxidant application on fat accumulation: preclinical evidence. Gonçalves AC, Nunes AR, Falcão A, Alves G, Silva LR.

Dietary Effects of anthocyanins in human health: a comprehensive review. Kimble R, Keane KM, Lodge JK, Howatson G. Dietary intake of anthocyanins and risk of cardiovascular disease: a systematic review and meta-analysis of prospective cohort studies.

Crit Rev Food Sci Nutr. Liang Y, Chen J, Zuo Y, Ma KY, Jiang Y, Huang Y, et al. Blueberry anthocyanins at doses of 0. Eur J Nutr. Yang L, Ling W, Du Z, Chen Y, Li D, Deng S, et al.

Effects of anthocyanins on cardiometabolic health: a systematic review and meta-analysis of randomized controlled trials. Mozos I, Flangea C, Vlad DC, Gug C, Mozos C, Stoian D, et al. Effects of Anthocyanins on Vascular Health.

Anthocyanins frequently interact with other phytochemicals, exhibiting synergistic biological effects but making contributions from individual components difficult to decipher. Over the past 2 decades, many peer-reviewed publications have demonstrated that in addition to their noted in vitro antioxidant activity, anthocyanins may regulate different signaling pathways involved in the development of CVD.

Limited yet promising data from epidemiological studies and human clinical trials are also presented. Abstract Anthocyanins are a group of abundant and widely consumed flavonoid constituents that occur ubiquitously in the plant kingdom, providing the bright red-orange to blue-violet colors present in many fruit- and vegetable-based food products.

Publication types Review.

New research links foods high in anthocyanins | EurekAlert! PubMed PubMed Central Google Carrdiovascular Erqou S, Anthocyanine S, Cardiocascular PL, Managing diabetes in older adults Angelantonio Carviovascular, Thompson A, Cardiovadcular IR, et al. Amthocyanins findings Five electronic databases were Cardiovascuar up to Glutathione oral supplements period of 1 Februaryyielding 13 eligible studies, including Wild salmon nutrition or cross-over clinical trials 18—59 years of ageusing PRISMA guidelines PROSPERO registration: CRD C-reactive protein induces release of both endothelial microparticles and circulating endothelial cells in vitro and in vivo: further evidence of endothelial dysfunction. Article CAS PubMed Google Scholar Hou D-X, Yanagita T, Uto T, Masuzaki S, Fujii M. Consumption of a flavonoid-rich açai meal is associated with acute improvements in vascular function and a reduction in total oxidative status in healthy overweight men. LOX uses arachidonic acid as substrate, catalyzing four different reactions such as 5S, 12R, 12S or 15S oxygenation [ ]. Int J Card Imaging.

Anthocyanins and cardiovascular health -

Source: Kimble R, Keane KM, Lodge JK, Howatson G. Dietary intake of anthocyanins and risk of cardiovascular disease: A systematic review and meta-analysis of prospective cohort studies. Critical Reviews in Food Science and Nutrition. Cherry Marketing Institute The Cherry Marketing Institute CMI is a not-for-profit organization funded by U.

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Journal Critical Reviews in Food Science and Nutrition. DOI Its mechanism is summarized in Fig. Today we have good predictor for this disease, associating its risk factor and biomarkers is possible to have an idea if a person will develop a CVD.

One of the greatest problem is to prevent and to treat those diseases, being important the investigation of new therapeutic agents. The dietary polyphenols, mainly anthocyanins, have shown some cardio protector activity, as will be discussed below.

Cardiovascular diseases: risk factors and molecular biomarkers. The main risk factors of cardiovascular disease are related to the oxidative stress, generating markers that are used to predict cardiovascular risk.

Anthocyanins are a subgroup of water-soluble pigments found in the major group of flavonoids that are responsible for colors ranging from red to blue in plants, flowers, seeds, fruits and other vegetal tissues [ 62 ], such as açaí Euterpe oleracea [ 63 ], strawberry Fragaria × ananassa [ 64 ], elderberry [ 65 ], chokeberry Aronia melanocarpa [ 66 , — ].

Thus, almost all species of angiosperms present anthocyanins [ 62 ]. They are similar molecules that have a benzoic ring linked to a non-benzoic ring with an oxygen atom inside in a condensed way.

There is yet another benzoic ring linked to those first two by a carbon—carbon bound C—C , this structure is known as 2-phenyl benzopyrylium cation or flavylium ion [ 6 ]. In each of those rings, named A-, B- and C-rings, there are seven different radicals in all of each valences and the variation of those said radicals that will differ the anthocyanidins, as shown in Fig.

Structural body of anthocyanidins. Structural body of anthocyanidins, ion flavilium composed of an aromatic ring A condensed with a non-aromatic ring C and another aromatic ring B forming a carbon—carbon bonding. Anthocyanins, the most common form of anthocyanidins in plants [ 67 ], contain the glycosylated flavylium ion [ 6 ].

There are more than known anthocyanidins [ 68 ]; however, there is up to different possibilities of anthocyanins, including the different types of anthocyanidins and the glycosylated part [ 69 ]. Nowadays, the use of polyphenolics, including anthocyanins, has been important in the treatment of chronic disease, such as CVD [ 4 ].

The pharmacologic action of these polyphenolics have been associated to the chemical structure of these compounds, as shown in Fig. Regarding to anthocyanins, several studies have shown their beneficial effects on CVD, inhibiting the inflammatory process, the endothelial dysfunction and NO production [ 70 , 71 ].

Oxidative stress constitutes a unifying mechanism of tissue injury leading to CVD. It occurs due an imbalance between the generation of ROS and RNS and the antioxidant defense systems in the body. These reactive species attack biomolecules such as lipids, DNA, and proteins enhancing the previously established tissue damage, as well as triggering cell death pathways [ 75 , 76 ].

ROS are a family of highly reactive species formed either enzymatically or no enzymatically in mammalian cells. They can cause cell damage either directly or through behaving as intermediates in diverse cell signaling pathways [ 76 ].

In the intact heart, the production of ROS occurs in three principal cells, endothelial cells, cardiomyocytes and neutrophils, or to pathway of the auto-oxidation of catecholamines [ 77 — 79 ].

Those free radicals are by-products of endogenous compounds or xenobiotics, provided from mechanisms like of the electron transport chain, nicotinamide adenine dinucleotide phosphate NADPH oxidase, xanthine oxidase XO , metabolism of the arachidonic acid and cytochrome P CYP [ 79 ].

Other sources of ROS may be reactions involving peroxisomal oxidases [ 80 , 81 ] CYP enzymes [ 79 , 82 ], NADPH oxidases [ 79 , 82 ], or XO [ 83 ]. Some work also elucidate that the production of ROS can be resulted of the mechanism of the monoamines oxidases and proteins p66 [ 70 , 84 ].

However, studies highlight that the major sources of ROS production in CVD are: mitochondrial, XO and NADPH oxidase pathways [ 84 ]. Comparing substitutions of different sugars, anthocyanins having glucose and galactose monosaccharides have higher antioxidant benefits regarding those containing disaccharides [ 86 , 87 ].

The antioxidant mechanisms of the anthocyanins typically include the suppression of reactive species formation, through enzyme inhibition or the sequestration of trace elements involved in the production of free radicals [ 88 ].

It is proposed that flavonoids interrupt the chain reaction of free radicals by donating hydrogen atoms to the peroxyl radical, forming a flavonoid radical. The flavonoid radical then reacts with the free radical ending, thus, propagation chain reaction [ 89 ]. The phenolic structure of anthocyanins allows for the donation of a proton belonging to a free radical, which regenerates the acyl glycerol molecule and stops oxidation by free radicals.

Thus, the phenol derivatives are transformed into free radicals and can stabilize and propagate without promoting oxidation reactions [ 92 ]. Several studies have reported the inhibitory action of anthocyanins in the XO pathway.

In this regard, one of the methods used to evaluate this effect in XO activity is measure the uric acid production, as described by Cos et al. Other determining factor to XO inhibitory action is the planarity of anthocyanins, which must contain the double bond between C-2 and C-3 positions and B ring that is coupled by conjugation to A and C rings.

Saturation of this double bond conjugation and destroy the coplanarity of the anthocyanins are responsible for inhibitory effect on the XO enzyme.

In this regard, Acquaviva et al. Thus, cyanidin and cyanidin 3- O -β- d -glucoside showed a protective effect on DNA cleavage, a dose-dependent free radical scavenging activity and an inhibition of XO activity.

Oxidative stress can be associated with iron storage protein, ferritin or heme proteins, which contribute to the initiation and propagation of lipid peroxidation. In addition, they also inhibit the oxidation of LDL induced by copper or by peroxyl radical [ — ].

Another important factor is that polyphenols with a catechol group can also bind metal ions. Bittar et al. A study reported that the anthocyanin, eggplant peels the delphinidin p -coumaroylrutinoside glucoside nasunin , has antioxidant potent activity by chelating ferrous-dependent mechanism.

The findings suggest that nasunin is a potent O 2 scavenger and has protective activity against lipid peroxidation [ ]. A chelating metal indirect mechanism of flavonoids was reported by Viana et al. Others mechanisms of anthocyanins not yet elucidated is the inhibition of apoptosis of macrophage induced by oxidized LDL.

Anthocyanins protect the skin against ultraviolet radiation UV [ ], helping to prevent photo-aging, combat hyperpigmentation induced by ultraviolet radiation, as well as have the ability to inhibit the synthesis of melanin by inhibiting the activity enzyme tyrosinase [ ].

This strong antioxidant activity is on the one hand the result of electron deficit in its chemical structure, and, secondly, the structure conjugate of anthocyanins, allowing the electronic delocalization leads to obtaining more stable radical products requiring further studies ratio structure and activity is acting in the inhibition of this enzyme.

Regarding to CVD, in vitro and in vivo studies showed that anthocyanins inhibit the oxidative stress involved in the atherosclerotic process [ ]. Since several mechanisms may be involved in this process, as the ability of anthocyanins inhibit LDL oxidation [ ] and reduce oxidative injury of vascular endothelial cells [ ].

The underlying mechanism remains unclear. Another pharmacologic effect of anthocyanin is its anti-inflammatory action in several disease, which is widely reported in studies about biomarkers of inflammation.

In this context, lipid mediators derived from arachidonic acid, as prostaglandins produced via cyclooxygenase COX -2 and leukotrienes via lipoxygenases LOX are important targets of anthocyanins [ , ].

Dreiseitel et al. PLA2 is a superfamily of esterases secreted by cells membranes that catalyze hydrolysis of sn-2 position of membrane glycerophospholipids to generate arachidonic acid as well others free fatty acids [ 4 ], precursor of prostaglandins and leukotrienes [ ].

Some members of the PLA2 family is lipoprotein-associated PLA2 and secretory PLA2 [ ], both the modified structures, complexed with LDL or HDL, have been shown to associate with oxLDL and activating various inflammatory pathways for atherogenesis and plaque rupture [ ].

COX are enzymes required for the conversion of n-6 fatty acids, mostly arachidonic acid, to prostanoids that play an important role in inflammation [ ]. Cyanidin has high inhibitory activity in these enzymes [ , ].

Another important enzyme inhibited by anthocyanins is LOX. In this sense, Knaup et al. LOX uses arachidonic acid as substrate, catalyzing four different reactions such as 5S, 12R, 12S or 15S oxygenation [ ].

The oxygenated substrates of these enzymes initiate biological reaction, activate cellular signaling through surface receptors or are metabolized to potent lipid mediators [ ]. Kuhn et al. Chronic inflammation is typical in vascular endothelial dysfunction triggered by the activation of certain factors such as nuclear factor NF -κB, which is functionally dependent on the cellular redox state.

In this context, the tumor necrosis factor TNF -α activates NF-κB signaling transduction what is considered involved in the pathogenic of atherosclerosis [ ]. Thereby, anthocyanins also act inhibiting NF-κB and NF-κB -dependent mediators. Paixão et al. Another research showed that malvidin inhibited the TNF-α, and it blocked the MCP-1, ICAM-1 and VCAM-1 expression induced by TNF-α [ ].

These authors also reported that the malvidin inhibited the psubunit NF-κB, suggesting that malvidin could block the degradation of IkB, a cytoplasm protein that regulates NF-κB. Others anthocyanins also have been reported to inhibit the TNF-α [ — ] and NF-κB [ ], as cyanidin O -glucoside.

Limtrakul et al. Vasodilation is a process to increase blood flow through endothelial cells that release vasodilators such as prostacyclin and NO, which has great influence on vascular tone [ 22 ]. It is also released by endothelium cells molecules that opposite NO function called vasoconstrictor molecules such as endothelin-1 ET-1 and angiotensin-2 [ 21 , 22 ].

The anthocyanins also have inhibitory action in vasodilators. Others studies related that the C3G inhibited the nitric oxide [ , ]. C3G, delphinidinglucoside and pelargonidinglucoside also were tested and they protected the ONOO· induced apoptotic on endothelial cells [ ].

All anthocyanin prevented ONOO· injury on endothelial cells through disrupting mitochondrial apoptotic pathway and inhibition of the Bax nuclear translocation [ ]. Martin et al. Some studies have also reported that anthocyanins had a stimulatory effect in the nuclear factor erythroid 2-related factor Nrf2 pathway.

The Nrf2 is an inducible transcription factor with a high sensitivity to oxidative stress located in the cytoskeleton, which is widely expressed in organs with hyperoxia consumption, such as the muscle, heart, vasculature, liver, kidney, brain, lung, skin, and digestive tract [ , ].

In humans, Nrf2 protein has amino acids, a molecular weight of 66 kDa and contains a basic region leucine zipper-type bZIP motif in its C-terminal domain [ , ]. Under normal conditions, Nrf2 is associated to an actin-bound protein, Keap1, but upon exposure to chemicals often electrophiles or ROS, the ubiquitin proteasome pathway ubiquitin E3 ligase promotes the Nrf2 degradation, thus the stabilized Nrf2 accumulates in the nucleus and transactivates the antioxidant response elements ARE -regulated target gene [ — ].

In this regard, Nrf2 is a key regulator of endogenous antioxidant and protective defense, including glutathione S-transferase GST and peroxidase GPx , NAD P H: quinoneoxidoreductase1 NQO-1 , hemeoxygenase-1 HO-1 , glutamate cysteine ligase GCL , γ-glutamylcysteine synthase GCS and glucose 6-phosphate dehydrogenase G-6PDH [ , , ].

Therefore, the Keap1-Nrf2 system protects cellular proteins and DNA from oxidative damage caused by ROS and electrophiles, due an upregulation of antioxidant enzymes and decreased sensitivity to oxidative stress damage related to inflammatory reactions, respiratory system and, cardiovascular diseases [ , ].

The physiological oxidative stress levels, related to CVD, activate weakly the Nfr2 [ ]. Thus, pharmacological interventions to enhance the efficiency of the induction of Nfr2 provide homeostatic mechanisms to increase its antioxidant activity.

In this regard, Soreti et al. Therefore, these authors suggested that the endothelial protection mechanism of C3G could also be associated with HO-1 induction, antioxidant enzyme regulated by Nrf2. In addition, another study with Aronia melanocarpa showed high levels of HO-1 in endothelial progenitor cells cultured with angiotensin II, and also the enhanced level of Nrf2 in a concentration-dependent manner [ ].

Recently, Pantan et al. Data showed the synergistic effect of atorvastatin and C3G enhanced the activation of the Nrf2 signaling pathway, promoting the activation heme oxygenase HO Animal models have proven successful in validating hypotheses with high accuracy when compared to human trials.

The compilation of the animal models in the next sections is showed in Table 1. As described above, anthocyanins have various pharmacologic actions.

Here, we report several studies involving the cardiovascular system performed in rat models. Shaughnessy et al. These authors concluded that food intake as BB may be used to combat hypertension and cardiovascular disease prevention.

Prior studies also have demonstrated a reduction in blood pressure after diet rich in antioxidants [ — ]. The consumption of a BB diet for 7 weeks was used by Kalea et al. The vasoconstriction induced by l -phenylephrine Phe in aorta rings was lowest in groups fed with BB, as well as antagonism of NO synthase caused a significant increase in vasoconstriction in both groups.

NO dependent vasodilation via endothelium induced by acetylcholine was higher in the experimental group.

The BB diet showed vasodilator and vasoconstrictor effect on the aorta and this was dependent of the NO metabolic pathway. Other findings also observed vasodilator effect of anthocyanins in the endothelium-dependent relaxation [ — ]. An anti-atherogenic effect of grape—bilberry was demonstrated by Graf et al.

Moreover, these authors investigated the distribution of fatty acids in plasma, and they observed decreased saturated fatty acids and increase of the long-chain n3-PUFA. Thus, the intake anthocyanins-rich juice of had beneficial effects in preventing atherosclerosis by improving endothelial function and serum lipid.

The lipid profile and oxidative stress were analyzed by Mohamed et al. and Morus nigra over the course of 4 weeks. In relation to oxidative stress, the authors observed a reduction in MDA and NO levels in the Morus alba L. These fruits also increased the total antioxidant capacity TEAC at all evaluated concentrations of blackberry fruit.

Regarding to lipid profile, there was significant reduction of total cholesterol, triacylglycerols, LDL and VLDL and increase in HDL in plasma in relation to control group. The consumption of blackberries rich in natural antioxidant could prevent the risk of onset of cardiovascular diseases, reducing the lipid profile and the oxidative stress.

Sankhari et al. on oxidative stress in heart and in liver. The results of the ingestion of anthocyanins by atherogenic rats showed effective decrease of glutathione GSH and elevation of the HDL-c level in serum, as well as the decrease of the cardiac creatinine kinase, creatinine kinase-MB, lactate dehydrogenase and hepatic markers aspartate transaminase and alanine transaminase compared to atherogenic rats.

In the oxidative stress in cardiac and hepatic tissues, the result demonstrated increase of the activities of superoxide dismutase SOD , Catalase, GSH and ascorbic acid. The levels of lipid peroxidation had significant decrease in the studied tissues, suggesting the cardioprotector and hepatoprotector effects of the anthocyanins.

Zawistowski, Kopecand and Kitts [ ] studied the onset of hypercholesterolemia in Wistar rats treated with an atherogenic diet, with the supplementation of a black rice Oryza sativa L. After this period, the treated groups with just the atherogenic diet presented accentuate hypercholesterolemia.

The results analyzed showed that the addition of black rice extract was capable to decrease the total cholesterol, LDL-c and triglycerides levels. However, there was not a significant difference in the levels of HDL-c. It was analyzed the decrease of total cholesterol concentration in the liver of the treated group, but there was not any significant difference in the heart or aorta.

Yang et al. This data showed that the ingestion of black rice was promisor in the reduction of the lipid profile in rats with hypercholesterolemia. Valcheva-Kuzmanova et al.

The serum levels of total cholesterol and LDL-c found lower levels in all the tested doses when compared with the control. Yet, the experimental groups did not show significant difference in HDL-c.

The results point to a possible heart protective effect of AMFJ, once it has in its composition phenolic compounds that might have antioxidant action, for example, the anthocyanins. Hypolipidemic and of oxidative stress effects were also shown in other studies [ , ].

Mauray et al. The mice were treated with a diet of anthocyanin-rich bilberry extract 0. The concentration of thiobarbituric acid-reactive substances TBARS , the plasma antioxidant capacity, total cholesterol and triacylglycerol were not showed significant difference between the treated groups.

In , Mauray et al. However, total cholesterol levels were reduced due to ingestion of anthocyanin-rich bilberry extract. Both studies showed that the anthocyanin extract was not able to reverse lipid index and oxidative stress, but there may be some fermented anthocyanins bioactive compounds to prove its positive results.

In the same year, Wang et al. This model showed reduction of total cholesterol levels and LDL-c, as well as high HDL-c level in experimental group; however, there was no significant difference in triglyceride levels.

In addition, theses authors also showed reduction of cholesterol concentration, 7-ketocholesterol 7-KC and 7-KC-cholesterol, and increase of ATP-binding cassette transporter G1 protein ABCG1 in aortic C3G animals.

The oxidative stress parameters analyzed showed reduction of SOD and lipid hydroperoxide in the treated group. Mice fed with C3G had increased phosphorylation of eNOS SER, leading the increase of concentration of nitrite and nitrate, and lower cGMP in the aorta. Thus, the treatment showed recovery in endothelial dysfunction, reduced atherosclerotic lesion, more ABCG1 expression, lowering of cholesterol level and 7-KC and an increase in cGMP concentration compared to the control.

However, no significant difference in triglyceride levels. Zhang et al. The consumption of C3G improved the impairment of endothelial function, lipid profile and prevention or treatment of diabetic vascular complications.

Xia et al. Wu et al. Anti-atherogenic effects and the reduction in inflammatory activity were analyzed by Wang et al. Reduction of inflammation by anthocyanins was also reported by Seymour et al. Yamakoshi et al.

The experimental group showed a lower hydroperoxide and MDA levels compared to control group. However, did not affect the lipid profile, suggesting the antioxidant activity of the polyphenol.

Finné Nielsen et al. In the final stage of 16 weeks of treatment was observed that the APE-treated group presented elevated cholesterol level and LDL in serum, while the BGJ group presented a reduction in VLDL.

Both groups presented elevation of SOD, beside the APE group elevated the glutathione peroxidase GPx level. There was no reduction in cholesterol accumulation the aorta of either group. The treatment with purified anthocyanin and black gooseberry juice presents conflicting results, suggesting further investigations to prove the results.

Kabiri et al. The animals were submitted to protocol of hypercholesterolemic diet during 45 days, after they received supplementation of A. The A.

caudatus extracts, considered an excellent source of anthocyanin and fibers, led to a meaningful regression of atherosclerosis area and decrease of total cholesterol, LDL, MDA and PCR levels in serum.

In comparison with the control group, the treated group also had an elevation of apolipoprotein and HDL-cholesterol, showing an effectiveness antioxidant activity. The supplementation with A. caudatus extract decrease the risk factors to CVD, due the hypercholesterolemic diet.

Abdel-Moemin [ ] also had positive results in the increase of HDL-C and lower hydroperoxides and thiobarbituric reactive substances concentrations when was used the treatment with black rice 25 g for 10 weeks.

Hypercholesterolemic rabbits were also used as a model by Sozański et al. Level of LDL and atherogenic index in plasma also were reduced in these treated animals, although it was not significant to cardiac risk and atherogenic coefficient in relation to control.

The expression of PPARα and GSH activity were elevated, SOD and GPx levels did not show difference. Thus, they suggested that the lipid peroxidation in the liver was diminished, due to inclusion of cornelian cherry to the diet.

Several human studies have confirmed the findings found in animal models, although the literature remains controversial [ , ]. Alvarez-Suarez et al. The participants should had cycles of dietary consumption of strawberry; they were advised to avoid strawberry and other polyphenols.

After these 10 days, the patients received the strawberry for 30 days g daily, and blood and urinary samples were collect. At the end of the 30 days, the patients were recommended to avoid strawberry for more 15 days. After these periods, again blood and urinary samples were collect to analyze.

The results demonstrated that after strawberry-supplemented patients presented decreased levels of cholesterol, LDL and triglyceride. These parameters returned to baseline levels after 15 days of the strawberry supplementation. The study also showed lower levels of spontaneous and oxidative hemolysis.

Thus, these authors concluded that the strawberry rich diet could partially protect the prevention of CVD. Qin et al. The patients were submitted to the treatment for 12 weeks. Blood parameters were measure before and after the period of 12 weeks with a fasting overnight.

In the blood analysis was observed increase of HDL-cholesterol and cholesterol efflux in serum in anthocyanin group compared to placebo. In contrast, the LHL-cholesterol and plasma cholesteryl ester protein CETP were decreased in the Anthocyanin group correlated to placebo.

In this study, the authors suggested that the decrease of LHL and increase of HDL is related the inhibition of the CETP. Thus, they concluded that the PON1 activity as associated to a better efflux of cholesterol and of cGMP, which can lead to improvement of the endothelium-dependent vasodilation through the activation of the NO-cGMP signaling pathway [ , ].

Using the same anthocyanin-purified extract, Hassellund et al. They used 27 subjects divided in two groups, a control placebo and the treated group. The patients in the treated group received a daily intake of mg of the purified extract for 4 weeks followed by a washout period of 4 weeks.

Those patients were physically examined after those period of time, including oscillometric blood pressure measurements, laboratory assessments, also doing stress tests, the both cold pressor test and mental stress test. The extract treated group presented no significant difference in the blood pressure and stress reactivity levels in relation to the control group.

This research analyzed common CVD markers and markers for oxidative stress. They stated that the HDL-cholesterol was modest increased in the patients treated with anthocyanin. Using an elderberry Sambucus nigra extract that contained mg of anthocyanin, Curtis et al.

This study involved 52 volunteers and they were separate in two groups, control and elderberry extract treated. The participants had blood samples collect to verify the CVD biomarkers; they also analyzed kidney and liver function, to access safety.

The treated group showed no significant changes in the cardiac biomarkers, neither in the liver and renal function. This data proved that the extract was safe however ineffective in altering the CVD biomarkers the period of the study [ 65 ].

In a study on blueberry, Basu et al. The study included men and women. The patients were divided in two group; one group was treated with 50 g of freeze-dried blueberry dissolved and reconstituted in mL of water and vanilla. In the control group, the patients were advised to consume water as control.

The patients were treated for 8 weeks with an evaluation after each 4-week period. This evaluation consisted of anthropometric and blood pressure measurements, the assessment of dietary intake and fasting blood draws.

The data showed a more significant reduction in blood pressure, oxLDL and serum MDA and hydroxynonenal; serum glucose concentration and lipid profiles showed no significant alteration.

These results suggest that blueberries have a correlation with CVD markers and improve aspects of metabolic syndrome. Basu et al. also investigated cranberry juice in a placebo-controlled trial. In this study, the authors observed changes in TEAC, oxLDL, MDA, inflammatory biomarkers PCR, interleukin-6 and lipid profiles for subjects with metabolic syndrome.

According to their finds, cranberry juice-treated patients had increased plasma antioxidant capacity, decreased oxiLDL and decreased MDA. However, in relation to PCR and interleukin-6, no significant alteration was observed in either group.

Another study based on cranberry juice was performed by Dohadwala et al. The authors investigated the effect of cranberry juice in subjects with coronary artery disease. In this crossover study, all subjects were submitted to noninvasive methods to examine the effect of cranberry juice on various measures of vascular function.

The data showed decreased aortic stiffness in comparison to the placebo group. Another important study was the one performed by Cassidy et al. In a double-blind study Naruszewicz et al. The study also stated a decrease in blood pressure and adiponectin levels.

Other studies have shown that chokeberry extract have capacity of reduction of SOD and platelet aggregation levels, lower arterial blood pressure and decrease inflammation in atherosclerosis [ 66 , — ]. The data collected are presented in Fig.

The bioactive compounds found in some plants produce positive effects that have been used in the medicinal field as potent new drugs for the treatment of several diseases, including CVD. This review showed that this fact remains true for the use of anthocyanins as potent drugs for the prevention of CVD due to inhibition the inflammatory process, the endothelial dysfunction and vasodilators production.

Human intervention studies and animal models using berries, vegetables, parts of plants and cereals either fresh or as juice or purified anthocyanin-rich extracts have demonstrated significant improvements in LDL oxidation, VLDL, CRP, Total Triglycerides, MDA, as well as, decreasing comorbidities.

Also, improving the clinical states of patients with CVD, showing that animal studies and humans trials have been successful in demonstrating the efficacy of anthocyanins to prevent and improve the life quality of CVD patients.

Despite of the potential benefit, there is still a need to standardize therapeutic strategies, such as appropriate effective dose, treatment time and relevant clinical laboratory parameters, which will allow the use of a large number of juice or purified anthocyanin-rich extracts as treatment or complement to existing treatment of CVD.

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Anthocyanins are flavonoids found in Anthocyanins and cardiovascular health large variety of foods. Anthpcyanins are Lifestyle weight loss triathlon nutrition guide widely consumed flavonoid and Anthocyqnins responsible cardiiovascular the beautiful red, purple, and Hypoglycemic unawareness warning signs coloring found in fruits, Anthcoyanins, grains, and Athocyanins. Aside from coloring our plate, they provide a large array of health benefits such as protection against liver injuries, reduction of blood pressure, improvement of eyesight, suppression of proliferation of cancer cells, and cardiovascular disease prevention Novotney ; Knczak and Zhang Anthocyanins have been used as traditional or folk medicine around the world. Only recently have we begun to research these health benefit claims. The role of anthocyanins in cardiovascular disease prevention is due to their protective oxidative stress properties. They are believed to act on different cells associated with the development of atherosclerosis. Zhang X, Wnd Y, Song F, Hydration strategies for hot weather endurance activities al. Effects cardiovasculr purified cardiovasclar supplementation on platelet chemokines in hypercholesterolemic individuals: a Anthocyanind controlled trial. Nutr Metab Lond. To assess Body shape fitness Anthocyanins and cardiovascular health 24 weeks of anthocyanin healtj on Cardiovxscular chemokines in hypercholesterolemic individuals; secondarily, to investigate if reductions in platelet chemokines effect changes in cholesterol or inflammatory markers. One hundred fifty hypercholesterolemic individuals were recruited, with 75 participants randomly assigned to the intervention group 31 males, 44 females and 75 to the placebo group 32 males, 43 females. After 24 weeks, participants completed the study 73 participants in each group. The study took place in China and all participants are presumed to be of Chinese decent. Anthocyanins and cardiovascular health

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