March 2014 Issue
Anthocyanins
By Densie Webb, PhD, RD
Today’s Dietitian
Vol. 16 No. 3 P. 20
These powerful compounds may help prevent CVD and cancer and boost cognitive function.
Many dietitians are well aware of the benefits fruits and vegetables provide, but few may know the actual names and types of the disease-fighting compounds they contain that are so important for good health.
Anthocyanins, a particular group of compounds, are one of the more than 6,000 members of the flavonoid family of polyphenol phytochemicals found in various plant foods.1 In addition to anthocyanins, the flavonoid group includes flavanols, flavones, flavanones, flavan-3-ols, and isoflavones. Anthocyanin pigments have been used in folk medicine for generations, but only recently the specific pharmacological properties of these compounds have been isolated and studied.2
There are many aspects to anthocyanins’ role in the body that remain a mystery, such as bioactivity, uptake, absorption, bioavailability, and distribution in the tissues. But laboratory research as well as studies in animals and humans have suggested that anthocyanins may play important roles in helping reduce the risk of cardiovascular disease (CVD), cognitive decline, and cancer. The role of anthocyanins in the prevention of these diseases has been linked to their antioxidant properties, but research now suggests that anthocyanins’ health benefits likely result from unidentified chemical properties beyond their antioxidant capacity.3
An Overview
Anthocyanins are plentiful in plant foods, providing the bright red-orange to blue-violet colors of many fruits and vegetables. These compounds occur naturally in plants in the form of glycosides, in which an anthocyanidin molecule is paired with a sugar. The part of the pigment that exists free of sugar (generically known as aglycone) is called an anthocyanidin.3 These compounds are most abundant in berries (eg, black currants, elderberries, blueberries, strawberries) and their juices, and in red and purple grapes, red wine, sweet cherries, eggplants, black plums, blood oranges, and red cabbage.
Plants produce anthocyanins as a protective mechanism against environmental stressors, such as ultraviolet light, cold temperatures, and drought. This production of anthocyanins in roots, stems, and especially leaf tissues is believed to provide resistance against these environmental hazards.
Moreover, anthocyanins are the most easily recognized and prominent flavonoid in the diet; the intake of these compounds is estimated to be as much as ninefold higher than that of other dietary flavonoids1—estimated to be between 3 and 215 mg/day.4 The amount of anthocyanins in foods can vary greatly. For example, Red Delicious apples provide more anthocyanins than Fuji apples; black raspberries are a far richer source than red raspberries; and Concord grapes are a much more concentrated source than red grapes.5
While the answers to how and why anthocyanins may help prevent disease remain undiscovered or unexplained, the literature to date is intriguing, and most researchers are calling for more studies to explore the potential health benefits of these naturally occurring compounds. “While one could argue that the evidence is inadequate to define a specific dietary recommendation, it’s clear that consuming anthocyanin-rich foods should be encouraged,” says Jeffrey Blumberg, PhD, director of the antioxidants research laboratory at the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University in Boston.
Cardiovascular Disease
Several studies have found an association between the consumption of anthocyanin-rich foods and CVD protection. As part of the Iowa Women’s Health Study, 34,489 postmenopausal women without CVD had their diets assessed and were followed for 16 years. The researchers found that consuming anthocyanin-rich strawberries and blueberries once per week was associated with a significant reduction in death from CVD and coronary artery disease.6 In addition, several epidemiologic studies have found an association between the consumption of red wine and decreased risk of death from CVD.6,7
Another study that assessed the effect of anthocyanins on health followed 87,242 women from the Nurses’ Health Study II; 46,672 women from the Nurses’ Health Study I; and 23,043 men from the Health Professionals Follow-Up Study for 14 years.8 Researchers found that those in the highest quintile of anthocyanin intake (mostly from blueberries and strawberries) had a significant 8% decreased risk in developing hypertension compared with those in the lowest quintile of anthocyanin intake. The risk reduction was even greater (12%) for those aged 60 or younger and, for all subjects, the decreased risk remained even after controlling for a large number of factors, including family history, physical activity, BMI, and other dietary factors associated with hypertension.
A larger group of 93,600 healthy women from the Nurses’ Health Study II was followed for 18 years; a high intake of anthocyanins was associated with a significant reduction in the risk of myocardial infarction.9 Specifically, those consuming more than three servings of blueberries and strawberries per week had a 34% lower risk compared with those who consumed fewer.
The decreased risk of CVD may be due, in part, to a reduction in arterial stiffness and blood pressure.10 Arterial stiffness is assessed based on the structure and function of arteries, and central systolic blood pressure is a strong predictor of atherosclerosis and the incidence of CVD.
As part of the Twins UK study of 1,898 women aged 18 to 75, researchers found that a higher intake of anthocyanins was associated with significantly lower central systolic blood pressure and arterial pressure. The authors suggested that consuming one to two portions of berries per day might be an important strategy for lowering CVD risk.10
A systematic review of clinical studies and meta-analyses on the effect of alcohol on CVD concluded that the polyphenolic compounds found in red wine, including anthocyanins, provide cardiovascular benefits that can’t be attributed to alcohol alone.11 However, recent studies have found that anthocyanin-rich black currant juice and blood orange juice had no effect on cardiovascular risk markers.12,13
A study of rats fed a red cabbage extract rich in anthocyanins recently provided the first piece of evidence that an anthocyanin extract protected against hypercholesterolemia induced by an atherogenic diet and related cardiac oxidative stress.14 Similar findings were obtained in a more recent study with rats that were fed a grape-bilberry juice rich in anthocyanins (15 mg/day or 50 mg/kg body weight—a physiological, not pharmacological dose) compared with those consuming an anthocyanin-depleted juice for 10 weeks.15 The animals consuming the grape-bilberry juice experienced reductions in serum cholesterol and triglyceride concentrations as well as increases in the proportion of polyunsaturated fatty acids and decreased saturated fatty acids.15
Laboratory studies suggest that anthocyanins and their metabolites, which are produced by gut microflora, may decrease inflammatory markers associated with increased CVD risk.4 Anthocyanins also may have antiplatelet activity.3
Cancer
Anthocyanins and anthocyanin-rich extracts in cell culture and in animals have anticarcinogenic activities. While laboratory studies have provided some insight into how they may work, the exact mechanism (or mechanisms) for how these dietary compounds prevent cancer is unclear. Laboratory studies that used a variety of cancer cells have indicated that anthocyanins not only act as antioxidants, they also activate detoxifying enzymes; prevent cancer cell proliferation; induce cancer cell death (apoptosis); have anti-inflammatory effects; have antiangiogenesis effects (ie, they inhibit the formation of new blood vessels that encourage tumor growth); prevent cancer cell invasion; and induce differentiation (the more differentiated the cancer cell, the less likely it is to grow and spread).16
In animal studies, anthocyanins inhibit cancer development in animals given carcinogens and in those with a hereditary predisposition to cancer.16 Anthocyanins have been tested against esophageal, colon, skin, and lung cancer, and in several cases have been effective against the development and progression of these cancers.16 In one study, freeze-dried black raspberries inhibited cell proliferation, inflammation, and angiogenesis of esophageal cancer cells in rats.17
In cell culture, anthocyanins from an anthocyanin-enriched purple sweet potato stopped the reproduction of colon cancer cells and initiated cancer cell death.18
Human studies have been less promising. Two studies from Italy found no relationship between anthocyanin intake and the risk of oral, pharyngeal, or prostate cancer.19,20 Another study examined the effect of supplementing the diets of young cancer patients receiving chemotherapy with 50 mg of anthocyanins, 40 mg of cysteine, and 200 mg of glutathione, and found no increased inhibition of tumor growth when compared to chemotherapy alone.21
However, in a study of 25 colon cancer patients who received 60 g/day of an anthocyanin-rich black raspberry powder for two to four weeks, the tumors had reduced proliferation rates and increased apoptosis.22 Another study of 25 colorectal cancer patients given 0.5 to 2 g/day of anthocyanins as a bilberry extract for seven days, found an improvement in several changes consistent with colorectal cancer chemoprevention.23 Paradoxically, the smallest dose of 0.5 g/day was most beneficial.
Cognitive Function
With regard to cognitive function, research suggests that flavonoids, including anthocyanins, have the ability to enhance memory and help prevent age-related declines in mental functioning.23 Extensive research in animals has shown that the flavonoids found in fruit and fruit juices can improve memory and slow age-related loss of cognitive functioning. Several other studies have found that berries, most notably blueberries, which are rich in anthocyanins, can effectively reverse age-related deficits in certain aspects of working memory. Anthocyanins and other flavonoids are thought to work by inhibiting neuroinflammation, activating synaptic signaling, and improving blood flow to the brain.3,24 It appears that some dietary anthocyanins can cross the blood-brain barrier, allowing the compounds to have a direct beneficial effect.25
The authors of a recent review on the subject suggested that the consumption of flavonoid-rich fruits such as berries, apples, and citrus throughout life potentially could limit or even reverse age-dependent deteriorations in memory and cognition. As of now, however, there are no human studies to prove a causal relationship between the consumption of anthocyanins, or any flavonoid, and cognitive functioning. Whether the consumption of flavonoid-rich foods can have a beneficial effect on cognition also may depend on when in life exposure occurs.
Anthocyanin Advice
The effects of anthocyanins are closely linked to their absorption and metabolism, but more research is needed to better understand how they’re absorbed and used in the body before anthocyanin doses can be prescribed for disease prevention.
“Eating enough fruits and veggies is a never-ending challenge,” says Jennifer Neily, MS, RDN, CSSD, LD, owner of Neily on Nutrition in Dallas. “I always encourage my clients to eat a rainbow of colors—red, orange/yellow, green, blue/purple—because of the disease-fighting benefits they provide.”
For anthocyanin-rich berries, she recommends keeping frozen ones on hand. “They’re great for a quick fiber-filled smoothie.”
Ximena Jimenez, MS, RDN, LD, a spokesperson for the Academy of Nutrition and Dietetics, says that while anthocyanins haven’t reached star status yet, consumers are starting to hear more about them. “Aim for three or more servings per week,” she recommends telling clients and patients. “Start your day with blueberries or blackberries, grape juice for lunch, and add eggplant, purple cauliflower, or purple onions to your favorite recipes.”
While Blumberg admits that the medical community has limited knowledge of the mechanisms of action and health benefits of anthocyanins, he questions the wisdom of waiting for definitive research when clients may benefit from increased consumption of anthocyanin-rich foods now.
— Densie Webb, PhD, RD, is a freelance writer, editor, and industry consultant based in Austin, Texas.
References
1. Wallace TC. Anthocyanins in cardiovascular disease. Adv Nutr. 2011;2:1-7.
2. Roy HJ, Lundy S, Eriksen C, Kalicki B. Anthocyanins. Pennington Nutrition Series. http://www.pbrc.edu/training-and-education/pdf/pns/pns_anthocyanins.pdf. 2009.
3. Tsuda T. Dietary anthocyanin-rich plants: biochemical basis and recent progress in health benefits studies. Mol Nutr Food Res. 2012;56(1):159-170.
4. Hidalgo M, Martin-Santamaria S, Recio I, et al. Potential anti-inflammatory, anti-adhesive, anti/estrogenic, and angiotensin-converting enzyme inhibitory activities of anthocyanins and their gut metabolites. Genes Nutr. 2012;7(2):295-306.
5. Wu X, Beecher GR, Holden JM, Haytowitz DB, Gebhardt SE, Prior RL. Concentrations of anthocyanins in common foods in the United States and estimation of normal consumption. J Agric Food Chem. 2006;54(11):4069-4075.
6. Mink PJ, Scrafford CG, Barraj LM, et al. Flavonoid intake and cardiovascular disease mortality: a prospective study in postmenopausal women. Am J Clin Nutr. 2007;85(3):895-909.
7. Rimm EB, Giovannucci EL, Willett WC, et al. Prospective study of alcohol consumption and risk of coronary disease in men. Lancet. 1991;338(8765):739-742.
8. Cassidy A, O’Reilly EJ, Kay C, et al. Habitual intake of flavonoid subclasses and incident hypertension in adults. Am J Clin Nutr. 2011;93(2):338-347.
9. Cassidy A, Mukamal KJ, Liu L, Franz M, Eliassen AH, Rimm EB. High anthocyanin intake is associated with a reduced risk of myocardial infarction in young and middle-aged women. Circulation. 2013;127(2):188-196.
10. Jennings A, Welch AA, Fairweather-Tait SJ, et al. Higher anthocyanin intake is associated with lower arterial stiffness and central blood pressure in women. Am J Clin Nutr. 2012;96(4):781-788.
11. Chiva-Blanch G, Arranz S, Lamuela-Raventos RM, Estruch R. Effects of wine, alcohol and polyphenols on cardiovascular disease risk factors: evidences from human studies. Alcohol Alcohol. 2013;48(3):270-277.
12. Jin Y, Alimbetov D, George T, Gordon MH, Lovegrove JA. A randomised trial to investigate the effects of acute consumption of a blackcurrant juice drink on markers of vascular reactivity and bioavailability of anthocyanins in human subjects. Eur J Clin Nutr. 2011;65(7):849-856.
13. Giordano L, Coletta W, Tamburrelli C, et al. Four-week ingestion of blood orange juice results in measurable anthocyanin urinary levels but does not affect cellular markers related to cardiovascular risk: a randomized cross-over study in healthy volunteers. Eur J Nutr. 2012;51(5):541-548.
14. Sankhari JM, Thunaojam MC, Jadeja RN, Devkar RV, Ramachandran AV. Anthocyanin-rich red cabbage (Brassica oleracea L.) extract attenuates cardiac and hepatic oxidative stress in rats fed an atherogenic diet. J Sci Food Agric. 2012;92(8):1688-1693.
15. Graf D, Seifert S, Jaudszus A, Bub A, Watzl B. Anthocyanin-rich juice lowers serum cholesterol, leptin, and resistin and improves plasma fatty acid composition in Fischer rats. PLoS One. 2013;8(6):e66690. doi:10.1371/journal.pone.0066690.
16. Wang LS, Stoner GD. Anthocyanins and their role in cancer prevention. Cancer Lett. 2008;269(2):281-290.
17. Wang LS, Hecht SS, Carmelia SG, et al. Anthocyanins in black raspberries prevent esophageal tumors in rats. Cancer Prev Res (Phila). 2009;2(1):84-93.
18. Lim S, Xu J, Kim J, et al. Role of anthocyanin-enriched purple-fleshed sweet potato p40 in colorectal cancer prevention. Mol Nutr Food Res. 2013;57(11):1908-1917.
19. Rossi M, Garavello W, Talamini R, et al. Flavonoids and the risk of oral and pharyngeal cancer: a case-control study from Italy. Cancer Epidemiol Biomarkers Prev. 2007;16(8):1621-1625.
20. Bosetti C, Bravi F, Talamini R, et al. Flavonoids and prostate cancer risk: a study in Italy. Nutr Cancer. 2006;56(2):123-127.
21. Bode U, Hasan C, Hulsmann B, Fleischhack G. Recancostat compositum therapy does not prevent tumor progression in young cancer patients. Klin Padiatr. 1999; 211(4):353-355.
22. Wang LS, Sardo C, Rocha CM, et al. Effect of freeze-dried black raspberries on human colorectal cancer lesions. Presented at: AACR Special Conference in Cancer Research: Advances in Colon Cancer Research; November 14-17, 2007; Cambridge, MA.
23. Thomasset S, Berry DP, Cai H, et al. Pilot study of oral anthocyanins for colorectal cancer chemoprevention. Cancer Prev Res (Phila). 2009;2(7):625–633.
24. Spencer JP. The impact of fruit flavonoids on memory and cognition. Br J Nutr. 2010;104 Suppl 3:S40-S47.
25. Youdim KA, Shukitt-Hale B, Joseph JA. Flavonoids and the brain: interactions at the blood-brain barrier and their physiological effects on the central nervous system. Free Radic Biol Med. 2004;37(11):1683-1693.