Red+Blue for Heart Protection
Abstract & Commentary
By Howell Sasser, PhD
Associate, Performance Measurement, American College of Physicians, Philadelphia, PA
Dr. Sasser reports no financial relationships relevant to this field of study. This article originally appeared in the March 2014 issue of Integrative Medicine Alert.
Synopsis: In a study of 93,600 women conducted over 18 years, those with the highest levels of anthocyanins in their diets had a risk of myocardial infarction 32% lower than those with the lowest levels, even after adjusting for other risk and protective factors.
Source: Cassidy A, et al. High anthocyanin intake is associated with a reduced risk of myocardial infarction in young and middle-aged women. Circulation 2013;127:188-196.
Researchers analyzed data from the nurses’ health Study II (NHSII), which began in 1989 with the enrollment of women between the ages of 25 and 42. Each participant completed a questionnaire about health events every 2 years and a questionnaire about dietary patterns every 4 years. Follow-up continued for a maximum of 18 years.
Participants who reported having had a myocardial infarction (MI), stroke, other kinds of cardiovascular disease, or cancer before the study period began were excluded. The outcomes of interest were nonfatal MI and fatal coronary heart disease. Reported events were confirmed with medical records whenever possible.
Intake of a number of subclasses of dietary flavonoids, including anthocyanins, flavanones, flavan-3-ols, flavones, flavonols, and polymers, was estimated mathematically from reported consumption of relevant foods. Supplement use was not reported. Intake levels for each 4-year interval were included in the study’s statistical models to allow for dietary changes over time. Other factors collected and used in the analysis to control for possible confounding included body mass index, physical activity, total energy intake, dietary fats, menopausal status, smoking, hormone use, and family history of MI. Secondary statistical models controlled for additional factors related to diet (potassium, folate, and fruit and vegetable intake) and health (hypertension, diabetes, angina, and hypercholesterolemia).
There were 405 cardiac events among 93,600 participants over 18 years of follow-up. There was a trend toward lower risk of MI with rising anthocyanin intake (P < 0.047), even after adjusting for potentially confounding factors. Those in the highest quintile of consumption had a risk 32% lower than those in the lowest quintile (hazard ratio, 0.68; 95% confidence interval, 0.49-0.96). For each 15 mg increase in consumption, the relative risk of MI declined by 17%. There also was evidence of some benefit with higher consumption of flavonols and flavonoid polymers, and with higher intake of flavonoid-containing foods, but these effects did not reach statistical significance.
COMMENTARY
The potential health benefit of foods, over and above their nutritional value, has been of interest since ancient times — Hippocrates said "Let your food be your medicine." The modern public is bombarded with advice about "superfoods" and advertisements promising miraculous results ("Eat this and never diet again!"). For a time, dietary supplements containing the active agents of various foods in concentrated form seemed promising, but careful research found little clinical benefit.1 What appears to remain is the observation that some constituent(s) of foods, perhaps even combinations of foods, have healthful properties when consumed in their original forms. Table 1 lists some common sources of the flavonoid subclasses that showed positive results in the present study.
Anthocyanins, a flavonoid subclass and one group of the phytochemicals responsible for the red and blue coloring of many fruits and vegetables, have strong antioxidant properties in vitro.2 However, this has not been found to correspond to strong antioxidant effects in vivo. Researchers speculate that anthocyanins and other flavonoids are too degraded by digestion to make their way into body tissue where they might scavenge free radicals. Instead, their effect may be achieved by stimulating other processes. In the case of the cardiovascular system, one theory is that anthocyanins increase the activation of nitric oxide synthase, which in turn affects vascular tone and inflammation.2 Alternatively, they may inhibit cell growth factors in the vascular endothelium.3 It should be noted that the present study did not have access to detailed medical information, and so could not shed any light on whether anthocyanin intake correlated with a reduced risk of atherosclerosis, or vascular spasm, or some other mechanism.
Regardless of this, if the mechanistic hypotheses are correct, relatively small quantities of anthocyanins may be needed to realize the potential benefit. This is significant because the typical American diet contains only small amounts — far less than in some dietary supplements.4 A study by Wu and colleagues found that while some foods contain large amounts of anthocyanins per unit of volume, data from the National Health and Nutrition Examination Survey showed that most Americans do not consume significant quantities of those foods. In the present study, the average anthocyanin intake was 2.5 mg/day in the lowest quintile of consumption and 25.1 mg/day in the highest. By comparison, some dietary supplements contain as much as 600 mg per dose.
This is important for the advice that clinicians might wish to give their patients. The present study demonstrated that measurable changes in risk could be achieved with relatively small dietary differences. Drawing on Wu et al’s data, the difference between the low and high anthocyanin intake quintile averages is equivalent to two plums, one serving of black beans, or half a serving of red grapes. Changes in eating patterns on this scale should seem manageable to many if not most patients. Choosing to increase one’s intake of anthocyanins in this way also has side benefits, such as increased consumption of dietary fiber, vitamins, and other phytochemicals, as well as perhaps crowding out some less healthy foods — in other words changing eating patterns.
Physicians and patients should bear in mind that it is these changes in patterns, rather than rigid adherence, that matter, as well as a consistent and long-term focus on a rainbow of colors in food. No one could — or should — eat an identical diet every day. Nor do foods contain precise and constant levels of any compound. Wu et al found anthocyanin levels in strawberries that varied from 35-69 mg per serving, and Table 2 gives examples of foods that contain several flavonoid subclasses in varying amounts.5-7 Dietary variety, including multiple sources of the same desirable substances, offers the best chance to maintain appropriate consumption through seasonal fluctuations in availability and phytochemical composition. While this method requires more planning and thought than simply taking a pill, it yields benefits that likely extend beyond what we yet understand.
Table 1. Common Sources of Anthocyanins, Flavonols, and Flavonoid Polymers.
| Flavonoid Subclass |
Common Sources in Food or Beverages |
| Anthocyanins |
- Blackberries
- Blueberries
- Cabbage, Red
- Cherries
- Concord Grapes
- Radishes, Red
- Raspberries, Black
- Raspberries, Red
|
| Flavonols |
- Capers
- Chocolate, Dark
- Fennel
- Tea, Black
- Tea, Green
- Hot Peppers
|
| Flavonoid Polymers |
- Chocolate, Dark
- Grapes, Red
- Tea, Black
- Wine, Red
|
Table 2. Comparative Flavonoid Content of Several Common Foods
| Food/Beverage Source |
Anthocyanins
(mg/100 g) |
Flavonols
(mg/100 g) |
Proanthocyanins*
(mg/100 g) |
| Blackberries |
89-211 |
13-19 |
6-47 |
| Blueberries |
67-183 |
1 |
88-261 |
| Grapes, Red |
25-92 |
2 |
44-76 |
| Plums |
2-25 |
1 |
106-334 |
| Strawberries |
15-75 |
- |
97-183 |
| Wine, Red |
1-35 |
1-55 |
24-70 |
*Proanthocyanins are a major class of flavonoid polymers, a group which also includes thearubigins and theaflavins.
References
- Kris-Etherton PM, et al. Antioxidant vitamin supplements and cardiovascular disease. Circulation 2004;110: 637-641.
- Lotito SB, Frei B. Consumption of flavonoid-rich foods and increased plasma antioxidant capacity of humans: Cause, consequence, or epiphenomenon? Free Radic Biol Med 2006;41:1727-1746.
- Oak MH, et al. Delphinidin and cyanidin inihibit PDGF(AB)-induced VEGF release in vascular smooth muscle cells by preventing activation of p38 MAPK and JNK. Br J Pharmacol 2006;149:283-290.
- Wu X, et al. Concentrations of anthocyanins in common foods in the United States and estimation of normal consumption. J Ag Food Chem 2006;54:4069-4075.
- Manach C, et al. Polyphenols: Food sources and bioavailability. Am J Clin Nutr 2004;79:727-747.
- Moyer RA, et al. Anthocyanins, phenolics, and antioxidant capacity in diverse small fruits: Vaccinium, rubus, and ribes. J Agric Food Chem 2002;50:519-525.
- Ryan JM, Revilla E. Anthocyanin composition of Cabernet Sauvignon and Tempranillo grapes at different stages of ripening. J Agric Food Chem 2003;51:3372-3378.
