Zhang X, Zhu Y, Song F, et al. Effects of purified anthocyanin supplementation on platelet chemokines in hypercholesterolemic individuals: a randomized controlled trial. Nutr Metab (Lond). 2016;13:86.
Randomized, double-blind, placebo-controlled trial
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.
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, 146 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. All participants were hypercholesterolemic, with cholesterol levels 200 to 310 mg/dL. Exclusion criteria included history of cardiovascular disease, high blood pressure, diabetes mellitus, thyroid disorder, smoking, or the use of any drug that could affect lipid parameters, inflammatory markers, or chemokines. All participants were advised to continue their regular diet and avoid high anthocyanin foods. At baseline, there was no significant difference in any of the measured parameters between the 2 groups.
Intervention was 2 anthocyanin capsules (Polyphenols AS, provided by Sandnes, Norway) taken twice a day (total dose of 320 mg anthocyanin per day) for 24 weeks. Placebo capsules were provided by the same manufacturer; the authors did not report the placebo’s content.
Fasting blood parameters for various platelet chemokine concentrations were obtained at baseline, 12 weeks, and 24 weeks. Lipids, high sensitivity C-reactive protein (hsCRP), and interleukin 1ß (IL-1ß) were also measured.
Overall, anthocyanin supplementation led to beneficial changes in platelet chemokines as well as favorable changes in lipids and inflammatory markers compared to placebo.
At week 12, only plasma CXCL5 (P=0.021) and CXCL8 (P=0.015) were significantly decreased compared to placebo. At week 24, there was a significant decrease in the mean values of platelet chemokines in the intervention vs placebo groups: CXCL7 (P=0.001), CXCL5 (P=0.011), CXCL8 (P=0.004), CXCL 12 (P=0.023) and CCL2 (P=0.001). There was no statistically significant difference in CXCL41, CXCL1, macrophage migration inhibitory factor (MIF), or plasminogen activator inhibitor 1 (PAI-1) concentrations between the 2 groups.
At week 24, mean high-density lipoprotein cholesterol (HDL-C) significantly increased (1.22 mmol/L at baseline to 1.37 mmol/L; P=0.018) and mean low-density lipoprotein cholesterol (LDL-C) significantly decreased (3.36 mmol/L to 3.01 mmol/L; P=0.036) compared to baseline values in the intervention group. Comparing the groups, there were also significant differences in the HDL-C (P=0.036) and LDL-C levels (P=0.030) at 24 weeks.
Compared to baseline levels, anthocyanin supplementation significantly reduced hsCRP and IL-1ß at week 12 (P<0.05). At week 24, IL-1ß but not hsCRP was statistically reduced from baseline. Comparison with the placebo group, however, led to significant decreases in plasma hsCRP (P=0.001), IL-1ß (P=0.019) and sP-selectin (P=0.027) at week 24.
Correlations with lipids
At week 24, positive correlations were found between CCL2 and CXCL7 levels and LDL-C levels (P=0.001 for each). Lastly, CXCL8 levels were negatively correlated with changes in the HDL-C in the intervention group (P<0.001).
Correlations with inflammatory markers
CXCL7 had positive correlations with hsCRP and IL-1ß (P<0.001 for each), CCL2 was positively correlated with hsCRP (P<0.001), CSCL12 significantly correlated with TNF-alpha (P<0.001), and there was a positive correlation between CXCL8 and sP-selectin levels (P<0.001).
No adverse interactions were reported in either of the 2 study groups.
Several studies have suggested that anthocyanins protect against atherosclerosis.1 More generally, evidence shows that eating anthocyanins may benefit those with high cholesterol, obesity, and/or inflammatory disorders.2-5 The authors of the current publication have previously shown that anthocyanin supplementation can reduce inflammatory markers and improve endothelial function.6-8 The current study under review fleshes out some of the mechanistic details underlying the protective benefits of anthocyanins on the endothelium.
Eat the rainbow of nature’s colors,’ or ‘Your plate is like an artist’s palate, it should have a variety of colors’ are easy ways to translate the data into practice.
Anthocyanins are a type of flavonoid, and all flavonoids are phenolic compounds (ie, polyphenols). Like many flavonoids, anthocyanins give the characteristic color to a variety of plants. Anthocyanin pigments mostly range from blue to red, which explains why many of the fruits, vegetables, and flowers high in anthocyanins appear purple. Some of these foods include eggplant, blueberries, blackberries, cherries, purple kohlrabi, violet petals, and beets. According to a 2017 review of anthocyanins in nature, there are at least “600 different naturally occurring anthocyanins that are widely distributed among at least 27 families, 73 genera and innumerable species.”9
While it is possible to recommend an anthocyanin supplement for patients, the question would be: Why? Given the abundance of blue/purple/red plant foods, surely any given patient can find anthocyanin-rich foods they like. Of course, whole food sources also contain thousands of other phytochemicals besides anthocyanins that we have yet to encapsulate in our reductionist quest for health. Many of these phytochemicals are thought to be synergistic, making whole plant consumption even more compelling.
The current study used 320 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 320 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.10 It contains data on 6 anthocyanins: cyanidin, delphinidin, malvidin, pelargonidin, peonidin, and petunidin. The database uses a uniform 100 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 53.64 mg of anthocyanins, frozen purple acai have 61.94 mg, and the white have 0.48 mg. 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 (160 mg); cranberries, raw (100 mg); and blackberries, raw (100 mg). Other foods include Concord grapes, raw (125 mg); red wine, syrah or shiraz (140 mg), radicchio, raw (127 mg anthocyanins per 100 g), and 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 210 mg anthocyanins per 100-gram serving. Once it’s cooked it has only 40 mg per 100 grams.
Of course, 100 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 150 grams. Given the high concentrations of anthocyanins in various foods and that the study showed measurable benefit at 320 mg, there is no reason to track closely. The simplest means of ensuring that people get enough anthocyanins is to encourage consumption of blue/purple/red foods at most meals and/or snacks. By doing so, 320 mg per day should be easily reached.
“Eat the rainbow of nature’s colors,” or “Your plate is like an artist’s palate, it should have a variety of colors” are easy ways to translate the data into practice.
My personal favorite way to describe which foods are rich in anthocyanins is to explain, “If it’s blue, purple, or red and occurs in nature, it’s probably high in anthocyanins. And, the worse the given food will stain a shirt, the higher the concentration.” Anthocyanins are pigments, so reminding patients that the color and the nutrient are one in the same is a simple fact many find inspiring.
- Wallace TC. Anthocyanins in cardiovascular disease. Adv Nutr. 2011;2:1-7.
- Afrin S, Gasparrini M, Forbes-Hernandez TY, et al. Promising health benefits of the strawberry: a focus on clinical studies. J Agric Food Chem. 2016;64(22):4435-4449.
- Edirisinghe I, Burton-Freeman B. Anti-diabetic actions of berry polyphenols - review on proposed mechanisms of action. J Berry Res. 2016;6(2):237-250.
- 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. J Berry Res. 2016;6(2):213-223.
- 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. 2014;25(3):289-294.
- 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. 2014;99(2):561-569
- Zhu Y, Xia M, Yang Y, et al. Purified anthocyanin supplementation improves endothelial function via NO-cGMP activation in hypercholesterolemic individuals. Clin Chem. 2011;57(11):1524-1533.
- 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. 2013;23(9):843-849
- Martín J, José Navas M, Jiménez-Moreno AM, Asuero AG. Anthocyanin Pigments: Importance, Sample Preparation and Extraction. In: Soto-Hernandez, ed. Phenolic Compounds - Natural Sources, Importance and Applications. InTech. https://www.intechopen.com/books/phenolic-compounds-natural-sources-importance-and-applications/anthocyanin-pigments-importance-sample-preparation-and-extraction. Published March 15, 2017. Accessed July 31, 2017.
- Bhagwat S, Haytowitz B. USDA Database for the Flavonoid Content of Selected Foods, Release 3.1. US Department of Agriculture, Agricultural Research Service. Nutrient Data Laboratory Home Page: http://www.ars.usda.gov/nutrientdata/flav. Accessed July 21, 2017.