Do all these phytochemicals in plant foods we hear about as antioxidants make any difference for health? In Part 1 of this series on antioxidant compounds, Navindra Seeram, PhD, and Alan Crozier, PhD, explained why laboratory tests such as ORAC, often used as the basis for labeling a food’s antioxidant power, should actually be considered simply an indicator of their relative content of polyphenol compounds…. (In other words, a measure of their content, not their effects). The bottom line is that most of these natural plant compounds are large molecules that can’t be absorbed out of our digestive tract. Other compounds form from them, however, that can be absorbed.
So the question now is, does this make any difference to our health? Here, in Part 2 of this interview series, Dr. Crozier explains some important research findings that help to answer this question.
Following the video, read on for a few other important pieces of the puzzle, and some thoughts on what this all means for healthful eating.
Plant Compounds’ Fate
Initially, when researchers wanted to see what happened to these compounds inside our bodies, they monitored a series of tests following single doses of foods or compounds. Plant foods like fruits, vegetables, whole grains, beans and nuts contain thousands of natural compounds called polyphenols, each metabolized somewhat differently. Overall, studies showed that a very small proportion of compounds like anthocyanins (the source of berries’ red and blue colors) from the food we eat are actually absorbed out of the digestive tract and carried through the body. Assuming that means these compounds can have no effect, however, is a mistake.
What happens to these flavonoid and other polyphenol compounds? Some are broken down, absorbed and circulated in the body as other compounds. Polyphenols that are not broken down and absorbed pass on to the colon, and we now see that the microbiota (bacteria) in our colon break down these plant compounds to forms that can be absorbed and circulated through the body. Research now shows that people differ in how they benefit from these compounds for several reasons:
♦ Ellagitannins are among the many polyphenol compounds in raspberries, strawberries, pomegranates and walnuts. Ellagitannins are poorly absorbed, but in the colon, they are broken down to ellagic acid, which is then metabolized to urolithins, compounds that are absorbed and demonstrate potential for important health protective effects. There are dramatic differences between people in urolithin production, and studies show that much of this is due to person-to-person differences in colon bacteria able to produce ellagic acid.
♦ Lignans, especially concentrated in flaxseed, are also found in a wide range of whole grains, vegetables, fruits, tea, coffee, legumes, nuts and seeds. Lignans from plant foods are broken down in the colon to compounds called enterolactone and enterodiol, which can be absorbed into the body and are under study for several potentially health-protective roles. Time in digestive tract may matter. Researchers say that people with digestive tracts in which things move through quickly may have less time to convert plant lignans to the absorbable compounds than people in whom things move more slowly.
♦ Studies show that overall, most of the metabolites (new compounds formed from the compounds in the plant foods we eat) circulate in our blood for only one-and-a-half to seven hours or so. That prompts me to wonder, might we benefit most when we include healthful plant foods throughout the day, rather than trying to cram a day’s worthy of good eating into one meal and “getting by” on less healthy choices the rest of the time?
♦ Making nutritious plant foods an everyday part of your healthy habits might even pay off in somehow getting more benefit from those foods. According to Wilhelmina Kalt, PhD, of Agriculture and Agri-Food Canada, preliminary results from small intervention trials show that in people consuming wild blueberry juice daily, compounds formed from anthocyanins may not be cleared as rapidly as seen in short-term studies of one-time consumption. If substantiated in further research, this would mean that higher levels of these compounds may circulate through the body when people regularly eat anthocyanin-rich foods (such as raspberries, blueberries, blackberries and strawberries) than what might be indicated by short-term studies.
Dr. Crozier’s Hamsters
In the video interview shared here, Dr. Crozier discusses experiments with a type of hamster that develops atherosclerosis over a short time in a manner so similar to humans that it offers a model to more quickly see the potential impact of our food choices. When fed a diet that has been shown to produce fatty streaks in a major blood vessel called the aorta (an early sign of developing heart disease), a wide range of foods high in polyphenol compounds significantly decreased formation of these fatty streaks. Dr. Crozier notes that although he had expected to identify particular “best choices”, he instead found that bilberries (a wild European blueberry), strawberries, raspberries, green tea and black tea all seem to offer potential protective effects.
In research elsewhere, when mice fed a high-fat diet that raised their blood cholesterol consumed naringenin, a flavonoid found especially in grapefruit, it reduced the formation of atherosclerotic plaque (the buildup in blood vessels that can lead to blockage) by about 40 percent. A closer look found changes in expression of genes that regulate several of the processes involved in creation and growth of this plaque.
Among mice in a study fed a standard diet, those given bilberry extract – rich in anthocyanin compounds—within a couple weeks showed that although antioxidant status in their blood did not change, cholesterol levels decreased. Researchers linked this bilberry addition to changes in expression of more than 1,000 genes, apparently affecting several processes that lead to atherosclerosis, including cholesterol metabolism, fat in the liver, and inflammation.
What about Humans?
We’ve noted that although most of the plant compounds that were originally hailed as antioxidants based on laboratory tests tend to be poorly absorbed, they are broken down to other compounds. And when the polyphenol-rich foods and drinks are fed to animals, researchers see evidence of health-protective effects. What about human studies?
One small randomized intervention trial involved people who all had metabolic syndrome (putting them at increased risk of heart disease and diabetes, as we’ve discussed here in Smart Bytes® many times before). One group ate a large daily amount of bilberries (similar to blueberries) substituted for other carbohydrate foods (so total calories stayed the same). With no change in body weight, a score summarizing several markers of inflammation decreased in eight weeks among the berry-eating group. When tested at 12 weeks, about a month after the berry-loaded diet ended, some markers of inflammation remained reduced, while hsCRP (among the most commonly tested markers of inflammation) had returned to starting levels.
- Of note, anthocycanin consumption was not the only change with the test diet. Dietary fiber consumption increased from a starting average of 24 grams a day (already much higher in this Finnish population compared to the U.S.) to an average of 32 grams a day. On the other hand, sugar consumption increased (as sucrose – table sugar – because the bilberry products used were sweetened), yet did not appear to lead to the negative effects you might expect to see in people with metabolic syndrome (who typically show some reduced ability to use insulin effectively).
- Further testing in a subgroup of participants in the study showed that as in the animal studies above, this anthocyanin-rich diet led to changes in expression of several genes.
- This study used a combination of berry puree and dried bilberries to provide people the equivalent of 400 grams of bilberries per day. That’s nearly 3 cups of berries a day — nearly seven times what the average person eats in Finland. The big question is whether such large intake is needed to achieve benefits. If we consistently eat a diet filled with foods providing a wide range of polyphenol compounds all day long, can we get similar health-protective effects?
In a large U.S. observational study (the Cancer Prevention Study-II Nutrition Cohort), among older adults with no history of heart attack, stroke or diabetes who were followed for seven years, higher flavonoid consumption was linked with less likelihood of heart disease death. Benefits were seen for most individual categories of flavonoids, not just one type in particular. And yes, those people with high flavonoid consumption – the highest consumers of vegetables and fruits—tended to be less overweight and have healthier lifestyles that those who consumed the least. Differences in risk factors like weight, smoking, physical activity and family history seemed to account for some of the heart health differences. Even after adjusting for these and other risk factors, however, those with highest flavonoid consumption had 18 percent fewer heart disease deaths than those with lowest flavonoid consumption.
- Results do not support the common assumption that if some is good, more and more is endlessly better. The biggest reduction in risk was seen simply by getting out of the lowest 20 percent of flavonoid consumption.
- Fruits and vegetables are major sources of flavonoids. People with lowest flavonoid consumption, showing the highest rate of heart disease deaths, averaged a total of four servings of vegetables and fruits a day; those with reduced risk averaged about six servings a day.
- If that seems daunting, before you run out to buy a flavonoid supplement …remember that high flavonoid consumption – especially from the variety of types associated with reduced heart disease deaths in this study – comes from consumption of a wide range of vegetables, fruits, whole grain, beans, nuts and seeds, as well as beverage choices like green and black tea, coffee, cocoa and red wine. We can’t assume that flavonoids alone get all the credit for that protection.
Researchers have discovered many benefits from a predominantly plant-based diet that includes a variety of nutrient-rich plant foods. This growing understanding of the role flavonoids and other polyphenol compounds may play in protecting health is simply adding to what we look for in a healthful diet.
The take-home message: Although most of the plant compounds that were originally hailed as antioxidants based on laboratory tests tend to be poorly absorbed, they are broken down to other compounds. We still have much to learn, but animal and human studies suggest that consuming polyphenol-rich foods and drinks offers potential to protect our health through a variety of mechanisms that extend far beyond antioxidant effects.
Come back for the third and final portion of this series to hear from Dr. Crozier and Dr. Seeram about what especially excites them about this research, and what it suggests about eating habits to promote health.
Chanet A, et al. Naringin, the major grapefruit flavonoid, specifically affects atherosclerosis development in diet-induced hypercholesterolemia in mice. J Nutr Biochem. 2012; 23(5):469-77.
Mauray A, et al. Bilberry anthocyanin-rich extract alters expression of genes related to atherosclerosis development in aorta of apo E-deficient mice. Nutr Metab Cardiovasc Dis. 2012; 22(1):72-80.
Kolehmainen M, et al. Bilberries reduce low-grade inflammation in individuals with features of metabolic syndrome. Mol Nutr Food Res. 2012; 56(10):1501-10.
McCullough ML et al. Flavonoid intake and cardiovascular disease mortality in a prospective cohort of US adults. Am J Clin Nutr 2012; 95(2): 454-464.