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Relation
Zhang X, Zhu Y, Song F, et al. Effects of purified anthocyanin supplementation on platelet chemokines in subjects with hypercholesterolemia: a randomized controlled trial.Nutr Metab (London). 2016;13:86.
Draft
Randomized, double-blind, placebo-controlled trial
Study objective
To evaluate the effects of 24 weeks of anthocyanin supplementation on platelet chemokines in individuals with hypercholesterolemia; second, to examine whether reductions in platelet chemokines cause changes in cholesterol or inflammatory markers.
Participant
One hundred and fifty individuals with hypercholesterolemia were recruited, with 75 participants randomly assigned to the intervention group (31 men, 44 women) and 75 to the placebo group (32 men, 43 women). After 24 weeks, 146 participants completed the study (73 participants in each group). The study took place in China and all participants are believed to be of Chinese descent. All participants were hypercholesterolemic with cholesterol levels of 200 to 310 mg/dL. Exclusion criteria included a history of cardiovascular disease, hypertension, diabetes mellitus, thyroid disease, smoking, or taking medications that could affect lipid parameters, inflammatory markers, or chemokines. All participants were advised to continue their normal diet and avoid foods high in anthocyanins. At baseline, there was no significant difference in any of the measured parameters between the 2 groups.
intervention
The intervention consisted of 2 anthocyanin capsules (Polyphenols AS, provided by Sandnes, Norway) taken twice daily (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 content of the placebo.
Target parameters
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.
Key insights
Overall, anthocyanin supplementation resulted in favorable changes in platelet chemokines as well as favorable changes in lipids and inflammatory markers compared to placebo.
Platelet chemokines
At week 12 only plasma CXCL5 (P=0.021) and CXCL8 (P=0.015) were significantly reduced compared to placebo. At week 24, there was a significant decrease in mean levels of platelet chemokines in the intervention vs. placebo group: 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 the levels of CXCL41, CXCL1, macrophage migration inhibitory factor (MIF), or plasminogen activator inhibitor 1 (PAI-1) between the two groups.
Lipids
At week 24, mean high-density lipoprotein cholesterol (HDL-C) increased significantly (1.22 mmol/L at baseline to 1.37 mmol/L;P=0.018) and the mean low-density lipoprotein cholesterol (LDL-C) decreased significantly (3.36 mmol/l to 3.01 mmol/l;P=0.036) compared to the baseline values in the intervention group. In the group comparison, there were also significant differences in HDL-C (P=0.036) and LDL-C levels (P=0.030) after 24 weeks.
Inflammatory markers
Compared to baseline values, 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. However, comparison with the placebo group resulted in significant decreases in plasma hsCRP (P=0.001), IL-1ß (P=0.019) and sP-selectin (P=0.027) in 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). Finally, CXCL8 levels were negatively correlated with changes in 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 study group.
Practice implications
Several studies have shown that anthocyanins protect against atherosclerosis.1More generally, evidence shows that consuming anthocyanins may benefit people with high cholesterol, obesity and/or inflammatory diseases.2-5The authors of the current paper have previously shown that anthocyanin supplementation can reduce inflammatory markers and improve endothelial function.6-8The study currently 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 simple ways to put the data into practice.
Anthocyanins are a type of flavonoid, and all flavonoids are phenolic compounds (i.e. polyphenols). Like many flavonoids, anthocyanins give a variety of plants their characteristic color. Anthocyanin pigments tend to range from blue to red, which explains why many fruits, vegetables, and flowers high in anthocyanins appear purple. Some of these foods include eggplant, blueberries, blackberries, cherries, purple kohlrabi, violet leaves and beets. According to a 2017 review of anthocyanins in nature, there are at least "600 different naturally occurring anthocyanins, widely distributed in at least 27 families, 73 genera, and countless species."9
While it is possible to recommend an anthocyanin supplement to patients, the question would be: why? Given the abundance of blue/purple/red plant foods, every patient can certainly find anthocyanin-rich foods that they like. Of course, in addition to anthocyanins, whole food sources also contain thousands of other phytochemicals that we have yet to encapsulate in our reductionist pursuit of health. Many of these phytochemicals are considered synergistic, which makes consuming whole plants even more attractive.
The current study used 320 mg of anthocyanins daily for just 24 weeks, with measurable benefits on cholesterol and inflammatory markers. If we recommend whole food sources, how do we figure out a daily dosage of 320 mg? Is that a portion of blueberries or a bucket?
A look at the United States Department of Agriculture (USDA) database on flavonoid content in foods is revealing.10It contains data on 6 anthocyanins: cyanidin, delphinidin, malvidin, pelargonidin, peonidin and petunidin. The database uses a consistent 100g serving for all anthocyanin amounts, making comparisons relatively easy. When looking at acai berries, there are three categories: purple, fresh; purple, frozen; and white, frozen. Fresh purple acai berries contain 53.64 mg of anthocyanins, frozen purple acai berries 61.94 mg and white 0.48 mg. This tells us that, as expected, anthocyanins are the purple in purple acai berries and that freezing may somehow increase their concentration (perhaps by reducing the water content).
While acai has become popular, berries grown 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 reduces anthocyanin concentration. Red cabbage is a good example of this. According to the USDA database, raw red cabbage contains 210 mg of anthocyanins per 100 gram serving. Once cooked it only has 40 mg per 100 grams.
Of course, 100 grams is a standardized amount used in the database and cannot be related to portions in a meal. To estimate this, a cup of blueberries weighs approximately 150 grams. Given the high concentrations of anthocyanins in various foods and the fact that the study showed measurable benefit at 320 mg, there is no reason to track this closely. The easiest way to ensure people are getting enough anthocyanins is to encourage consumption of blue/purple/red foods at most meals and/or snacks. In this way, 320 mg per day should be easily achieved.
“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 put the data into practice.
My personal favorite way to describe which foods are high 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 stains a shirt, the higher the concentration." Anthocyanins are pigments, so reminding patients that the color and the nutrient are one and the same is inspiring for many.