Components in red raspberries may have anti-inflammatory, anti-oxidative and metabolic stabilizing activity, according to a comprehensive review of the available scientific literature published in the January issue of Advances in Nutrition. These properties shed light on the potential role of red raspberries in helping to reduce the risk of metabolically-based chronic diseases, including cardiovascular disease, diabetes mellitus, obesity, and Alzheimer’s disease: all of which share critical metabolic, oxidative, inflammatory links.
Red raspberries contribute a number of valuable essential nutrients, including providing an excellent source of vitamin C and nine grams of fiber per cup. They are also among the few plant foods that provide a source of ellagitannins and anthocyanins in the same package. The evidence is suggesting that the action of these nutrients and phytochemicals in the body hold the key to red raspberry’s health promoting properties.
“Turns out what is good for the heart, is also good for the brain. That is what is particularly interesting about the research on red raspberries – their potential to help reduce factors contributing to metabolic syndrome which has implications for diabetes development and overall cardiovascular and brain health,” says Britt M. Burton-Freeman, PhD, MS of the Center for Nutrition Research, Institute for Food Safety and Health, Illinois Institute of Technology, and lead author of the paper.
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Red raspberries are naturally rich in polyphenols, and as a result of recently published research, scientists are now beginning to understand how and why these polyphenols may offer human health benefits.
According to lead researcher Dr Alan Crozier, at the department of nutrition, University of California, Davis: “In order to further study the potential health benefits of red raspberry consumption, it is important to first understand how the body metabolises raspberry polyphenols, and the mode of action of the bioactive compounds that underlie these potential protective effects.”
Polyphenols are a class of phytochemicals. Polyphenols in red raspberries include: anthocyanins, flavan-3-ols, procyanidins, flavonols, ellagitannins, and hydroxycinnamates.
Animal and cellular studies examining how phytochemicals may work at the molecular level, suggest that certain phytochemicals may help slow age-related declines which can also impact a person’s disease risk. A growing body of research is focused on how some phytochemicals may offer protection against some cancers, heart disease, stroke, high blood pressure, cataracts, osteoporosis and other chronic health conditions. While current evidence is promising, additional long term studies are needed to establish the role of berry polyphenols in the prevention of specific health conditions.
Crozier and colleagues were interested in the fate of ellagitannins and anthocyanins, the compounds thought to be involved in beneficial health effects, following ingestion of the berries by human volunteers. Their study looked at how these phytochemicals are metabolized by the body once ingested.
To determine this, researchers asked human volunteers to consume 300 grams of raspberries (a little over 2 cups) and then have their blood and urine samples analysed over a 24 hour period. Analysis of these samples by high performance liquid chromatography and mass spectrometry showed an array of phytochemicals metabolites in the blood: some that peaked in the blood within 1-1.5 h, others at 6 h and still other metabolites peaking at 24 h after raspberry consumption. The work of Crozier and colleagues illustrate the complex metabolism of raspberry phytochemicals and that they are absorbed in the small intestine and the colon, which play an important role in the bio-availability of both anthocyanins and ellagitannins.
“The information discovered in our research is of importance as it enables other investigators to test these metabolites in cell-based model systems relating to cardiovascular function, colonic health and various cancers, in order to determine the mode of action of the bioactive compounds. This is critical to understanding the potential effects of raspberry consumption,” says Crozier.
A second study looked at how the metabolites of ellagitannins, called urolithins, were able to reduce the inflammatory response in rat heart muscle cells exposed to high glucose concentrations – a model which mimics a condition common in people with diabetes mellitus and hyperglycemia (high blood sugar). Overtime, this inflammation produces oxidative stress and may play a role in the development of diabetic cardiomyopathy, which can lead to heart failure. The results of this research suggest that ellagitannin-rich foods such as red raspberries, pomegranates, blackberries, strawberries and walnuts may support heart cell function. However, additional research is needed in order to determine if these compounds would have the same effect in humans.
“While this study shows the potential of ellagitannins/urolithins’ ability to help maintain normal function in the diabetic heart, further human studies are needed,” said Dr Danielle Del Rio at the department of food science, University of Parma, Italy. “In particular, the influence of a mix of circulating metabolites on the inflammatory scenario should be taken into account, and specifically designed intervention studies aimed at assessing the impact of ellagitannin-rich food sources on markers for inflammation should be performed.”
Red raspberries, containing ellagitannins and cyanidin-based anthocyanins, were fed to volunteers and metabolites appearing in plasma and urine were analysed by UHPLC-MS. Anthocyanins were not absorbed to any extent with sub nmol/L concentrations of cyanidin-3-O-glucoside and a cyanidin-O-glucuronide appearing transiently in plasma. Anthocyanins excreted in urine corresponded to 0.007% of intake. More substantial amounts of phase II metabolites of ferulic acid and isoferulic acid, along with 4′-hydroxyhippuric acid, potentially originating from pH-mediated degradation of cyanidin in the proximal gastrointestinal tract, appeared in urine and also plasma where peak concentrations were attained 1–1.5 h after raspberry intake. Excretion of 18 anthocyanin-derived metabolites corresponded to 15.0% of intake, a figure substantially higher than obtained in other anthocyanin feeding studies. Ellagitannins pass from the small to the large intestine where the colonic microbiota mediate their conversion to urolithins A and B which appeared in plasma and were excreted almost exclusively as sulfate and glucuronide metabolites. The urolithin metabolites persisted in the circulatory system and were excreted in urine for much longer periods of time than the anthocyanin metabolites although their overall urinary recovery was lower at 7.0% of intake. It is events originating in the proximal and distal gastrointestinal tract, and subsequent phase II metabolism, that play an important role in the bioavailability of both anthocyanins and ellagitannins and it is their metabolites which appear in the circulatory system, that are key to elucidating the mode of action(s) underlying the protective effects of these compounds on human health.
Diabetic cardiomyopathy (DCM) develops independently of common cardiovascular co-morbidities and is initiated by the metabolic derangements accompanying diabetes mellitus, including hyperglycaemia, which may cause a mild inflammatory state able to negatively affect myocardial biochemistry, structure, and function. This work shows how different urolithins, ellagitannin-derived metabolites, were able to modulate the pro-inflammatory mediators and growth factors secreted by rat cardiac myocytes and fibroblasts exposed to high glucose concentrations. At 1 µM concentration, coherent with dietary exposure to ellagitannin-rich foods, urolithins B and B-glucuronide succeeded in preventing inflammatory responses in cardiomyocytes, while in fibroblasts urolithin D was the most effective in controlling the overexpression of fractalkine, among the tested inflammatory mediators. Urolithins underwent extensive biotransformations in both cell types, including (de)glucuronidation, methylation, and sulphation. This suggests that the inflammatory bulk produced by hyperglycaemia could be attenuated by the regular intake of ellagitannin-rich foodstuffs such as pomegranates, raspberries, blackberries, strawberries, and walnuts.