Dr Louis Bherer, Ph. D., NeuropsychologueProfesseur titulaire au Département de Médecine de l’Université de Montréal. Directeur du Centre ÉPIC de l’Institut de cardiologie de Montréal.4 January 2023
- Participants in a study who had a high dietary intake of flavonols had slower cognitive decline than those who had a lower intake.
- Higher total flavonol intake was associated with a significantly slower decline in episodic memory, semantic memory, perceptual speed and working memory.
- Among the flavonols, kaempferol and quercetin were associated with slower cognitive decline, but not myricetin and isorhamnetin.
Flavonoids are polyphenolic compounds found in plants and in large quantities in fruits and vegetables in particular. These compounds are best known for their anti-inflammatory and antioxidant properties. Flavonoids have been associated in several previous studies with slowing age-related cognitive decline and dementia. However, few studies have attempted to identify which flavonoid subclasses and individual molecules are most active in protecting brain health. A recently published American study provides some answers by evaluating the effect of the intake of total flavonols and individual flavonols (kaempferol, quercetin, myricetin, isorhamnetin) on the cognitive performance of the elderly.
The study was conducted among 961 participants from the city of Chicago in the United States, aged 60 to 100, who were part of the Rush Memory and Aging Project cohort, and who were followed for 6.9 years on average. The participants, whose average age was 81 at the start of the study, were mostly female (75%), Caucasian (98%), and had an average of 15 years of schooling. Participants’ diet was assessed using a validated semi-quantitative questionnaire, and dietary flavonol intake was inferred from the collected data. The participants’ cognitive performance was assessed annually with a battery of 19 standardized tests.
A higher dietary intake of total flavonols and individual flavonols was associated with a lower rate of overall cognitive decline and several cognitive domains. A higher intake of total flavonols was associated with a slower decline in episodic memory (memories of personal events), semantic memory (memory of facts and concepts), perceptual speed, and working memory (short-term memory), but had no effect on visuospatial construction ability (understanding and representation of space in 2 and 3 dimensions).
Analysis of individual flavonols indicates that higher intakes of kaempferol and quercetin are associated with slower cognitive decline. In contrast, myricetin and isorhamnetin were not associated with an effect on global cognitive decline. Kale, beans, tea, spinach and broccoli were the foods highest in kaempferol among those consumed in this study. Tomatoes, kale, apples and tea were the foods highest in quercetin in this study.
The mechanisms underlying this favourable association are not yet well understood. The study authors suggest that the anti-inflammatory properties of flavonols may decrease the amplitude or duration of neuroinflammation. In addition, the antioxidant properties of flavonols could reduce or even prevent cell damage caused by oxidative stress, which generates reactive oxygen derivatives (free radicals, oxygenated ions, peroxides).
An earlier study by the same group of researchers reported that green leafy vegetables (spinach, kale, collard greens, lettuce) and certain constituents including kaempferol were associated with slowing overall cognitive decline. The authors concluded that “eating about one serving per day of green leafy vegetables and foods high in phylloquinone, lutein, nitrate, folate, α-tocopherol, and kaempferol may help slow cognitive decline with age.”
The protective role of certain flavonols on cognition has been demonstrated in animal models. Thus, quercetin supplementation improves memory and learning in transgenic mice used as an animal model of Alzheimer’s disease. In another study, kaempferol and myricetin improved memory and learning and reduced oxidative stress in mice used as a model of Alzheimer’s disease.
The prospective design of the American study does not make it possible to establish a causal link between dietary flavonol intake and cognition. Randomized clinical trials would confirm the role of flavonols on cognitive performance and, in the longer term, the prevention of cognitive decline associated with age. This type of study would also make it possible to clarify the dose-response relationship for optimal brain health. In any case, the study also has several strong points: a large number of participants, duration of the study, robust measurement of cognition by the 19 cognitive tests, validated questionnaires. The results were adjusted to minimize residual confounders, since it is possible that a higher dietary intake of flavonols is an indirect effect of a healthier diet. Among the limitations of this study are: self-reported food intake is subject to recall bias; because of their advanced age, participants are at risk of mild cognitive impairment that could cause errors when answering food questionnaires; there remains a possibility of reverse causation (cognitive decline may have altered participants’ eating habits). According to the authors, additional analyses (sensitivity analyses), however, indicate that reverse causation is unlikely.
The results of this study suggest that the consumption of fruits and vegetables (especially green leafy vegetables) in the elderly may not only help them maintain good health in general, but also delay or prevent cognitive decline. However, more studies are needed to confirm and better understand how flavonols slow cognitive and memory decline.
Dr Martin Juneau, M.D., FRCPCardiologue et Directeur de la prévention, Institut de Cardiologie de Montréal. Professeur titulaire de clinique, Faculté de médecine de l'Université de Montréal. / Cardiologist and Director of Prevention, Montreal Heart Institute. Clinical Professor, Faculty of Medicine, University of Montreal.14 October 2021
- Dietary lignans are phenolic compounds that come mainly from plant-based foods, especially seeds, whole grains, fruits, vegetables, wine, tea and coffee.
- Consumption of lignans is associated with a reduced risk of developing cardiovascular disease, according to several well-conducted studies.
There are over 8,000 phenolic and polyphenolic compounds found in plants. These compounds are not nutrients, but they have various beneficial biological activities in the human body. They are generally grouped into 4 classes: phenolic acids, flavonoids, stilbenes (e.g., resveratrol), and lignans. Lignans are dimers of monolignols, which can also be used in the synthesis of a long branched polymer, lignin, found in the walls of the conductive vessels of plants. From a nutritional standpoint, lignins are considered to be a component of insoluble dietary fibre.
Figure 1. Structures of the main dietary lignans
Dietary lignans, the most important of which are matairesinol, secoisolariciresinol, pinoresinol and lariciresinol, come mainly from plant-based foods, particularly seeds, whole grains, fruits, vegetables, wine, tea and coffee (see Table 1). Other lignans are found only in certain types of food, such as medioresinol (sesame seeds, rye, lemon), syringaresinol (grains), sesamin (sesame seeds). Lignans are converted into enterolignans by the gut microbiota, which are then absorbed into the bloodstream and distributed throughout the body.
Table 1. Lignan content of commonly consumed foods.
Adapted from Peterson et al., 2010 and Rodriguez-Garcia et al., 2019.
Several studies indicate that lignans can prevent cardiovascular disease and other chronic diseases, including cancer, and improve cardiovascular health, through its anti-inflammatory and estrogenic properties (the ability to bind to estrogen receptors).
A recently published US study indicates that there is a significant association between dietary intake of lignans and the incidence of coronary heart disease. Among the 214,108 people from 3 cohorts of healthcare professionals, those who consumed the most lignans (total) had a 15% lower risk of developing coronary heart disease than those who consumed little. Considering each lignan separately, the association was particularly favourable for matairesinol (-24%), compared to secoisolariciresinol (-13%), pinoresinol (-11%), and lariciresinol (-11%). There is a nonlinear dose-response relationship for total lignans, matairesinol, and secoisolariciresinol with a plateau (maximum effect) at approximately 300 µg/day, 10 µg/day, and 100 µg/day, respectively. Canadians consume an average of 857 µg of lignans per day, enough to benefit from the positive effects on cardiovascular health, but residents of some Western countries such as the United Kingdom, the United States and Germany do not have an optimal intake of lignans (Table 2).
The favourable association for lignans was especially apparent among participants who had a high dietary fibre intake. The authors of the study suggest that fibre, by supporting a healthy microbiota, may promote the production of enterolignans in the gut.
Table 2. Daily intake of lignans in Western countries.
Adapted from Peterson et al., 2010.
PREDIMED (Prevención con Dieta Mediterránea), a recognized study conducted among over 7,000 Spaniards (55–80 years old) at high risk of developing cardiovascular disease, compared the Mediterranean diet (supplemented with nuts and extra virgin olive) to a low-fat diet advocated by the American Heart Association for the prevention of cardiovascular disease (CVD). In this study, the Mediterranean diet was clearly superior to the low-fat diet in preventing CVD, so the study was stopped after 4.8 years for ethical reasons. Further analysis of the PREDIMED data showed that there is a very favourable association between a high dietary intake of polyphenols and the risk of CVD. Participants who consumed the most total polyphenols had a 46% lower risk of CVD than those who consumed the least. The polyphenols that were most strongly associated with reduced risk of CVD were flavanols (-60%), hydroxybenzoic acids (-53%), and lignans (-49%). It should be noted that the nuts and extra virgin olive oil that were consumed daily by participants in the PREDIMED study contain appreciable amounts of lignans.
Another analysis of data from the PREDIMED study showed a favourable association between total polyphenol intake and the risk of death from any cause. A high intake of total polyphenols, compared to a low intake, was associated with a 37% reduction in the risk of premature mortality. Stilbenes and lignans were the most favourable polyphenols for reducing the risk of mortality, by 52% and 40%, respectively. In this case, flavonoids and phenolic acids were not associated with a significant reduction in mortality risk.
No randomized controlled studies on phenolic compounds and the risk of CVD have been performed to date. There is therefore no direct evidence that lignans protect the cardiovascular system, but all the data from population studies suggests that it is beneficial for health to increase the dietary intake of lignans and therefore to eat more fruits, vegetables, whole grains, legumes, nuts and extra virgin olive oil, which are excellent sources of these still too little known plant-based compounds.
Dr Martin Juneau, M.D., FRCPCardiologue et Directeur de la prévention, Institut de Cardiologie de Montréal. Professeur titulaire de clinique, Faculté de médecine de l'Université de Montréal. / Cardiologist and Director of Prevention, Montreal Heart Institute. Clinical Professor, Faculty of Medicine, University of Montreal.23 November 2020
- Chronic inflammation is actively involved in the formation and progression of plaques that form on the lining of the arteries, which can lead to the development of cardiovascular events such as myocardial infarction and stroke.
- Two studies show that people whose diet is anti-inflammatory due to a high intake of plants (vegetables, fruits, whole grains), beverages rich in antioxidants (tea, coffee, red wine) or nuts have a significantly lower risk of being affected by cardiovascular disease.
- This type of anti-inflammatory diet can be easily replicated by adopting the Mediterranean diet, rich in fruits, vegetables, legumes, nuts and whole grains and which has repeatedly been associated with a lower risk of cardiovascular events.
Clinically, the risk of having a coronary event is usually estimated based on age, family history, smoking and physical inactivity as well as a series of measures such as cholesterol levels, blood sugar level and blood pressure. The combination of these factors helps to establish a cardiovascular disease risk “score”, i.e. the likelihood that the patient will develop heart disease over the next ten years. When this score is moderate (10 to 20%) or high (20% and more), one or more specific drugs are generally prescribed in addition to recommending lifestyle changes in order to reduce the risk of cardiovascular events.
These estimates are useful, but they do not take into account other factors known to play an important role in the development of cardiovascular disease. This is especially true for chronic inflammation, a process that actively participates in the formation and progression of plaques that form on the lining of the arteries and can lead to cardiovascular events such as myocardial infarction and stroke.
The clinical significance of this chronic inflammation is well illustrated by studies of patients who have had a heart attack and are treated with a statin to lower their LDL cholesterol levels. Studies show that a high proportion (about 40%) of these people have excessively high blood levels of inflammatory proteins, and it is likely that this residual inflammatory risk contributes to the high rate of cardiovascular mortality (nearly 30%) that affects these patients within two years of starting treatment, despite a significant reduction in LDL cholesterol. In this sense, it is interesting to note that the canakinumab antibody, which neutralizes an inflammatory protein (interleukin-1 β), causes a slight but significant decrease in major cardiovascular events in coronary patients. Statins, used to lower LDL cholesterol levels, are also believed to have an anti-inflammatory effect (reduction in C-reactive protein levels) that would contribute to reducing the risk of cardiovascular events. One of the roles of inflammation is also demonstrated by the work of Dr. Jean-Claude Tardif of the Montreal Heart Institute, which shows that the anti-inflammatory drug colchicine significantly reduces the risk of recurrence of cardiovascular events.
Reducing chronic inflammation is therefore a very promising approach for decreasing the risk of cardiovascular disease, both in people who have already had a heart attack and are at a very high risk of recurrence and in healthy people who are at high risk of cardiovascular disease.
Two studies published in the Journal of the American College of Cardiology suggest that the nature of the diet can greatly influence the degree of chronic inflammation and, in turn, the risk of cardiovascular disease. In the first of these two articles, researchers analyzed the link between diet-induced inflammation and the risk of cardiovascular disease in 166,000 women and 44,000 men followed for 24 to 30 years. The inflammatory potential of the participants’ diet was estimated using an index based on the known effect of various foods on the blood levels of 3 inflammatory markers (interleukin-6, TNFα-R2, and C-reactive protein or CRP). For example, consumption of red meat, deli meats and ultra-processed industrial products is associated with an increase in these markers, while that of vegetables, fruits, whole grains and beverages rich in antioxidants (tea, coffee, red wine) is on the contrary associated with a decrease in their blood levels. People who regularly eat pro-inflammatory foods therefore have a higher inflammatory food index, while those whose diet is rich in anti-inflammatory foods have a lower index.
Using this approach, the researchers observed that a higher dietary inflammatory index was associated with an increased risk of cardiovascular disease, with a 40% increase in risk in those with the highest index (Figure 1). This increased risk associated with inflammation is particularly pronounced for coronary heart disease (acute coronary syndromes including myocardial infarction) with an increased risk of 46%, but seems less pronounced for cerebrovascular accidents (stroke) (28% increase in risk). The study shows that a higher dietary inflammation index was also associated with two risk markers for cardiovascular disease, higher circulating triglyceride levels as well as lower HDL cholesterol. These results therefore indicate that there is a link between the degree of chronic inflammation generated by diet and the risk of long-term cardiovascular disease, in agreement with data from a recent meta-analysis of 14 epidemiological studies that have explored this association.
Figure 1. Change in the risk of cardiovascular disease depending on the inflammatory potential of the diet. From Li et al. (2020). The dotted lines indicate the 95% confidence interval.
A second study by a group of Spanish researchers investigated the anti-inflammatory potential of walnuts. Several epidemiological studies have reported that regular consumption of nuts is associated with a marked decrease in the risk of cardiovascular disease. For example, a recent meta-analysis of 19 prospective studies shows that people who consume the most nuts (28 g per day) have a lower risk of developing coronary artery disease (18%) or of dying from these diseases (23%). These reductions in the risk of cardiovascular disease may be explained in part by the decrease in LDL cholesterol (4%) and triglyceride (5%) levels observed following the consumption of nuts in intervention studies. However, this decrease remains relatively modest and cannot alone explain the marked reduction in the risk of cardiovascular disease observed in the studies.
The results of the Spanish study strongly suggest that a reduction in inflammation could greatly contribute to the preventative effect of nuts. In this study, 708 people aged 63 to 79 were divided into two groups, a control group whose diet was completely nut free and an intervention group, in which participants consumed about 15% of their calories daily in the form of walnuts (30–60 g/day). After a period of 2 years, the researchers observed large variations in the blood levels of several inflammatory markers between the two groups (Figure 2), in particular for GM-CSF (a cytokine that promotes the production of inflammatory cells) and interleukin-1 β (a highly inflammatory cytokine whose blood levels are correlated with an increased risk of death during a heart attack). This reduction in IL-1 β levels is particularly interesting because, as mentioned earlier, a randomized clinical study (CANTOS) has shown that an antibody neutralizing this cytokine leads to a reduction in the risk of myocardial infarction in coronary heart patients.
Figure 2. Reduction in blood levels of several inflammatory markers by a diet enriched with nuts. From Cofán et al. (2020). GM-CSF: granulocyte-monocyte colony stimulating factor; hs-CRP: high-sensitivity C-reactive protein; IFN: interferon; IL: interleukin; SAA: serum amyloid A; sE-sel: soluble E-selectin; sVCAM: soluble vascular cell adhesion molecule; TNF: tumour necrosis factor.
Taken together, these studies therefore confirm that an anti-inflammatory diet provides concrete benefits in terms of preventing cardiovascular disease. This preventative potential remains largely unexploited, as Canadians consume about half of all their calories in the form of ultra-processed pro-inflammatory foods, while less than a third of the population eats the recommended minimum of five daily servings of fruits and vegetables and less than 5% of the recommended three servings of whole grains. This imbalance causes most people’s diets to be pro-inflammatory, contributes to the development of cardiovascular diseases as well as other chronic diseases, including certain common cancers such as colon cancer, and reduces the life expectancy.
The easiest way to restore this balance and reduce inflammation is to eat a diet rich in plants while reducing the intake of industrial products. The Mediterranean diet, for example, is an exemplary anti-inflammatory diet due to its abundance of fruits, vegetables, legumes, nuts and whole grains, and its positive impact will be all the greater if regular consumption of these foods reduces that of pro-inflammatory foods such as red meat, deli meats and ultra-processed products. Not to mention that this diet is also associated with a high intake of fibre, which allows the production of anti-inflammatory short-chain fatty acids by the intestinal microbiota, and of phytochemicals such as polyphenols, which have antioxidant and anti-inflammatory properties.
In summary, these recent studies demonstrate once again the important role of diet in preventing chronic disease and improving healthy life expectancy.
Dr Martin Juneau, M.D., FRCPCardiologue et Directeur de la prévention, Institut de Cardiologie de Montréal. Professeur titulaire de clinique, Faculté de médecine de l'Université de Montréal. / Cardiologist and Director of Prevention, Montreal Heart Institute. Clinical Professor, Faculty of Medicine, University of Montreal.28 May 2020
- Asians have a much lower incidence of cardiovascular disease than North Americans, a difference that has been attributed, at least in part, to their high consumption of soybeans.
- This protection is due to soy’s high content of isoflavones, a class of polyphenols that have several positive effects on the cardiovascular system.
- A recent study carried out among 210,700 Americans (168,474 women and 42,226 men) has just confirmed this reduction in the risk of coronary heart disease associated with the consumption of soybeans, illustrating how this legume is an attractive alternative to meat as a source of protein.
It has been known for several years that people in Asian countries have a much lower incidence of cardiovascular disease than in the West. The study of migrant populations has shown that this difference is not due to genetic factors. For example, an analysis carried out in the 1970s revealed that the Japanese who had emigrated to California had twice the incidence of coronary heart disease than that of their compatriots who remained in Japan. It should be mentioned that these Asia-America differences are also observed for several types of cancer, in particular breast cancer. Asian women (China, Japan, Korea) have one of the lowest incidences of breast cancer in the world, but this cancer can become up to 4 times more common as a result of their migration to America, and its incidence even becomes similar to that of third generation Americans. The rapid rise in cardiovascular disease or cancer following migration to the West therefore suggests that abandoning the traditional lifestyle of Asians for the one in vogue in North America greatly favours the development of these diseases.
One of the differences between the Asian and North American lifestyles that has long interested researchers is the huge gap in soy consumption. While an average of 20 to 30 g of soy protein is consumed daily in Japan and Korea, this consumption barely reaches 1 g per day in the United States (Figure 1). It is proposed that this difference could contribute to the higher incidence of cardiovascular disease in the West for two main reasons:
- Like all members of the legume family (lentils, peas, etc.), soy is an excellent source of fibre, vitamins, minerals, and polyunsaturated fats, nutrients known to be beneficial to heart and vessel health;
- Soybeans are an exceptional source of isoflavones, a class of polyphenols found almost exclusively in this legume. The main isoflavones in soybeans are genistein, daidzein and glycitein (Figure 2), these molecules being present in varying amounts depending on the degree of processing of soybeans.
Figure 1. Comparison of the amounts of soybeans consumed daily by people in different countries. From Pabich and Materska (2019).
Figure 2. Molecular structures of the main isoflavones. Note that equol is not present in soy products, but is rather generated by the gut microbiome following their ingestion.
The highest concentrations of isoflavones are found in the starting beans (edamame) and foods derived from fermented beans (natto, tempeh, miso), while foods from the pressing of beans (tofu, soy milk) contain slightly less (Table 1). These foods are commonly consumed by Asians and allow them to obtain isoflavone intakes varying from 8 to 50 mg per day, depending on the region, quantities clearly greater than those of the inhabitants of Europe and America (less than 1 mg per day). It should be noted, however, that soy is gradually becoming more and more popular in the West as an alternative to meat and that isoflavone intake can reach levels similar to Asians (18–21 mg per day) in certain groups of health-conscious people.
Table 1. The isoflavone content of various foods. Source: United States Department of Agriculture, Nutrient Data Laboratory.
The importance of a high intake of isoflavones comes from the multiple biological properties of this class of molecules. In addition to their antioxidant and anti-inflammatory activities, common to many polyphenols, a unique feature of isoflavones is their structural resemblance to estrogens, the female sex hormones, and it is for this reason that these molecules are often referred to as phytoestrogens. This estrogenic action has so far been mainly studied in relation to the development of hormone-dependent breast cancers. Since the growth of these cancers is stimulated by estrogens, the presence of phytoestrogens creates a competition that attenuates the biological effects associated with these hormones, especially the excessive growth of breast tissue (this mode of action is comparable to that of tamoxifen, a drug prescribed for several years against breast cancer). It is also important to note that, contrary to a very widespread misconception, the consumption of soybeans should not be discouraged for women who have survived breast cancer. On the contrary, many studies conducted in recent years clearly show that regular soy consumption by these women is absolutely safe and is even associated with a significant decrease in the risk of recurrence and mortality from this disease. It should be mentioned that despite the similarity of isoflavones to estrogens, studies indicate that soy does not interfere with the effectiveness of tamoxifen or anastrozole, two drugs frequently used to treat hormone-dependent breast cancers. Consequently, for people who have been affected by breast cancer, there are only benefits to incorporating soy into their diet.
Several data suggest that the positive effect of isoflavones on health is not limited to their anticancer action, and that the combination of the antioxidant, anti-inflammatory and estrogenic activities of these molecules may also contribute to the cardiovascular benefits of soy (Table 2).
Table 2. Main properties of isoflavones involved in reducing the risk of cardiovascular disease associated with soy consumption.
A cardioprotective effect associated with soy consumption is also suggested by the results of an epidemiological study recently published in Circulation. By examining the eating habits of 210,700 Americans (168,474 women and 42,226 men), the researchers found that people with the highest isoflavone intake (about 2 mg per day on average) had a risk of coronary heart disease decreased by 13% compared to those with minimal intake (0.15 mg per day on average). A protective effect is also observed for tofu, with an 18% reduction in the risk of coronary heart disease for people who consume it once or more per week compared to those who ate it very rarely (less than once per month). Regular consumption of soy milk (once or more per week) is also associated with a slight decrease in risk, but this decrease is not statistically significant.
These reductions may seem modest, but it should be noted that the amounts of soybeans consumed by participants in this study are relatively small, well below what is commonly measured in Japan. For example, in a Japanese study that reported a 45% decrease in the risk of myocardial infarction in women who consumed the most soy, the isoflavone intake of these people was on average around 40 mg/day, i.e. 20 times more than in the American study (2 mg/day). It is therefore likely that the reductions in the risk of coronary heart disease observed in the United States represent a minimum and could probably be greater as a result of higher soy intake.
An interesting aspect of the decreased risk of coronary heart disease associated with tofu is that it is observed as much in younger women before menopause as in postmenopausal women, but only if they are not using hormone therapy (Figure 3). According to the authors, it is possible that after menopause, the estrogenic action of isoflavones compensates for the drop in estrogen levels and may mimic the cardioprotective effect of these hormones. In the presence of synthetic hormones, on the other hand, isoflavones are “masked” by excess hormones and therefore cannot exert their beneficial effects. For younger women, it is likely that the higher expression of the estrogen receptor before menopause promotes a greater interaction with isoflavones and allows these molecules to positively influence the function of blood vessels.
Figure 3. Association between risk of coronary heart disease and tofu consumption by hormonal status.
From Ma et al. (2020).
Taken together, these observations suggest that soy products have a positive effect on cardiovascular health and therefore represent an excellent alternative to meat as a source of protein. A recent study reports that these cardiovascular benefits can be even more pronounced following the consumption of fermented soy products such as natto, which is very rich in isoflavones, but given its texture (sticky, gooey), its strong smell (reminiscent of a well-made cheese), and its low availability in grocery stores, this food is foreign to our food culture and unlikely to be adopted by the North American population. Tofu is probably the most accessible soy-derived food given its neutral taste that allows it to be used in a wide variety of dishes, Asian-style or not. Soy milk is a less attractive alternative, not only because its consumption is not associated with a significant decrease in the risk of coronary heart disease, but also because these products often contain significant amounts of sugar.
Dr Martin Juneau, M.D., FRCPCardiologue et Directeur de la prévention, Institut de Cardiologie de Montréal. Professeur titulaire de clinique, Faculté de médecine de l'Université de Montréal. / Cardiologist and Director of Prevention, Montreal Heart Institute. Clinical Professor, Faculty of Medicine, University of Montreal.1 August 2018
Berries are becoming increasingly popular in our diet, whether consumed fresh, frozen, dried or canned, and in related products such as jams, jellies, yogurts, juices and wines. Berries provide significant health benefits because of their high content of phenolic compounds, antioxidants, vitamins, minerals and fibres. Recognizing these health benefits has recently led to a 21% increase in world berry production.
The generic term “berries” is sometimes used to refer to small fruits, but from a botanical point of view, if some berries are genuineberries (blueberries, bilberries, cranberries, currants, lingonberries, elderberries), others are polydrupes (raspberries, blackberries), and the strawberry is a “false fruit” since the achenes (the small seeds on the outer surface of the strawberry) are the actual fruits of the strawberry. Berry fruits are rich in phenolic compounds such as phenolic acids, stilbenes, flavonoids, lignans and tannins (see the classification and structure of these compounds in Figure 1). Berries are particularly rich in anthocyanidins, pigments that give the skin and flesh of these fruits their distinctive red, blue or purple colour (Table 1).
Figure 1. Classification and chemical structure of phenolic compounds contained in berries. Adapted from Parades-López et al., 2010 and Nile & Park, 2014.
Like most flavonoids, anthocyanidins are found in nature as glycosides (compounds made of a sugar and another molecule) called anthocyanins. These anthocyanins can be absorbed in their whole form (linked to different sugars) both in the stomach and in the intestine. Anthocyanins that reach the large intestine can be metabolized by the microbiota (intestinal flora). The maximum concentration of anthocyanins in the bloodstream is reached from 30 minutes to 2 hours after eating berries. However, the maximum plasma concentration (1–100 nmol/L) of anthocyanins is much lower than what is measured in intestinal tissues, indicating that these compounds are metabolized extensively before entering the systemic circulation as metabolites. After administering a radiolabelled anthocyanin to humans, 35 metabolites were identified, 17 in blood, 31 in urine and 28 in feces. Thus, it is likely that these metabolites, rather than the intact molecule, are responsible for the health benefits associated with anthocyanins.
Table 1. Content of phenolic compounds, flavonoids, and anthocyanins of different berries. Adapted from Parades-López et al., 2010 and Nile & Park, 2014.
|Berries (genus and species)||Phenolic compounds||Flavonoids||Anthocyanins
|(mg/100 g fresh fruit)||(mg/100 g fresh fruit)||(mg/100 g fresh fruit)
|Raspberry (Rubus ideaous)||121||6||99
|Blackberry (Rubus fruticosus)||486||276||82–326
|Strawberry (Fragaria x. ananassa)||313||–||54
|Blueberry (Vaccinium corymbosum)||261–585||50||25–495
|Bilberry (Vaccinium myrtillus )||525||44||300
|Cranberry (Vaccinium macrocarpon)||315||157||67–140
|Redcurrant (Ribes rubrum)||1400||9||22
|Blackcurrant (Ribes nigrum)||29-60||46||44
|Elderberry (Sambucus nigra)||104||42||45-791
|Red cranberry (Vitis vitis-idea)||652||74||77
Biological activities of berries
Data from in vitro and animal experimental models indicate that the phenolic compounds in berries may produce their beneficial effects through their antioxidant, anti-inflammatory, antihypertensive, and lipid-lowering activities, which could prevent or mitigate atherosclerosis. Perhaps the best-known of the biological activities of phenolic compounds is their antioxidant activity, which helps protect the body’s cells from damage caused by free radicals and counteract certain chronic diseases associated with aging. According to several studies using in vitro and animal models, berries also have anti-cancer properties involving several complementary mechanisms such as induction of metabolic enzymes, modulation of the expression of specific genes and their effects on cell proliferation, apoptosis (programmed cell death, an unsettled process in cancer cells), and signalling pathways inside the cell.
In a prospective study conducted in China with 512,891 participants, daily consumption of fruit (all types of fruit) was associated with an average decrease in systolic blood pressure of 4.0 mmHg on average, a decrease of 0.5 mmol/L of blood glucose concentration, a 34% reduction in the risk of major coronary events and a 40% reduction in the risk of cardiovascular mortality. These results were obtained by comparing participants who ate fruits daily to those who did not consume them at all or very rarely. In this study, there was a strong dose-response correlation between the incidence of cardiovascular events or cardiovascular mortality and the amount of fruit consumed. Studies suggest that among the constituents of fruit, it is the flavonoids, and especially the anthocyanins, that are responsible for these protective effects.
A number of prospective and cross-sectional studies have examined the association between the consumption of anthocyanins and cardiovascular risk factors (see this review). In four out of five studies that examined the risks of coronary heart disease or nonfatal myocardial infarction, anthocyanin consumption was associatedwith a reduction in coronary artery disease risk from 12% to 32%. The impact of anthocyanins on the risk of stroke was investigated in 5 studies, but no evidence of a protective effect was found in this case.
With respect to cardiovascular risk factors, studies indicate that higher consumption of anthocyanins is associated with decreased arterial stiffness, arterial pressure, and insulinemia. The decrease in blood pressure associated with the consumption of anthocyanins, -4 mmHg, is similar to that seen in a person after quitting smoking. The effect of anthocyanins on insulin concentration, an average reduction of 0.7 mIU/L, is similar to the effects of a low-fat diet or a one-hour walk per day. A decrease in inflammation has been associated with the consumption of anthocyanins and flavonols, a mechanism that may underlie the reduction of cardiovascular risk and other chronic diseases.
Randomized controlled trials
A systematic review and meta-analysis of 22 randomized controlled trials, representing 1,251 people, report that berry consumption significantly reduces several cardiovascular risk factors, such as blood LDL cholesterol , systolic blood pressure , fasting glucose concentration , body mass index , glycated haemoglobin , and tumour necrosis factor alpha , a cytokine involved in systemic inflammation. In contrast, no significant changes were observed for the other markers of cardiovascular disease that were tested: total cholesterol, HDL cholesterol, triglycerides, diastolic blood pressure, ApoAI, ApoB, Ox-LDL, IL-6, CRP, sICAM-1,and sICAM-2.
Another systematic review published in 2018 evaluated randomized controlled trials on the effects of berry consumption on cardiovascular health. Among the 17 high-quality RCTs, 12 reported a beneficial effect of berry consumption on cardiovascular and metabolic health markers. Four out of eleven RCTs reported a reduction in systolic and/or diastolic blood pressure; 3/7 studies reported a favourable effect on endothelial function; 2/3 studies reported an improvement in arterial stiffness; 7/17 studies reported beneficial effects for the lipid balance; and 3/6 studies reported an improvement in the glycemic profile.
Berries and cognitive decline
Greater consumption of blueberries and strawberries was associated with a slowdown in cognitive decline in a prospective study of 16,010 participants in the Nurses’ Health Study aged 70 or older. Consumption of berries was associated with delayed cognitive decline of approximately 2.5 years. In addition, nurses who had consumed more anthocyanidins and total flavonoids had a slower cognitive decline than participants who consumed less.
The exceptional content of phenolic compounds in berries and their positive effects on health remind us that the quality of food is not just about nutrients: proteins, carbohydrates, lipids, vitamins and minerals; a wide variety of other molecules found in plants are absorbed from the intestines and routed through the bloodstream to all cells in the body. While not essential nutrients, phytochemicals such as flavonoids can contribute to better cardiovascular health and healthier aging.
Dr Martin Juneau, M.D., FRCPCardiologue et Directeur de la prévention, Institut de Cardiologie de Montréal. Professeur titulaire de clinique, Faculté de médecine de l'Université de Montréal. / Cardiologist and Director of Prevention, Montreal Heart Institute. Clinical Professor, Faculty of Medicine, University of Montreal.14 May 2017
Updated on July 13, 2018
A recent study published in Nature Medicine suggests that coffee consumption may protect the heart and blood vessels due to the anti-inflammatory effect of caffeine. As we age, a slowing metabolism, combined with increased oxidative stress, causes the body to accumulate several inactive metabolites that are considered toxic to the immune system and activate the inflammatory response. Chronic inflammation is very harmful to the cardiovascular system, as it promotes the progression of several phenomena that damage the heart and blood vessels, such as atherosclerosis, hypertension and insulin resistance. Researchers have observed that people who regularly consume caffeinated drinks, particularly coffee, produce less of these inflammatory metabolites, have more elastic blood vessels, and are on average healthier.
These results are in line with several epidemiological studies showing that regular coffee consumption is associated with the reduced risk of cardiovascular disease and mortality in general. For example, a meta-analysis of studies involving 1,279,804 participants found that people who consumed a moderate amount of coffee (3 to 5 cups per day) were about 15% less likely to be affected by cardiovascular disease (coronary heart disease and stroke) than people who never drank coffee.
Several studies have also shown that coffee consumption is safe for people with established coronary heart disease. For example, a randomized clinical trial involving patients who had suffered a heart attack with acute ST-segment elevation (STEMI) showed that coffee consumption (4 to 5 cups per day, for a caffeine intake of 353 mg) did not cause arrhythmia and was not associated with any cardiovascular disorder. These observations are consistent with other studies showing that coffee consumption is not associated with the development of arrhythmias such as atrial fibrillation, and may even be associated with a decreased risk of such events.
Coffee also does not seem to have any major effects on blood pressure, although caffeine is known to stimulate the sympathetic nervous system. Studies show that, in individuals who never drink coffee, caffeine can indeed cause a short-term increase in blood pressure (by about 10 mm Hg), but the effect is transient and disappears completely in regular drinkers due to the phenomenon of tolerance. The absence of the long-term hypertensive effect of coffee was confirmed by a study involving 155,594 women showing that the regular consumption of coffee, even in high amounts (6 cups per day), is not associated with an increased risk of hypertension. However, the same study reported that the consumption of other sources of caffeine such as soft drinks (regular and diet) is associated with an increased risk of high blood pressure, suggesting that there are other compounds in coffee that may offset the effect of caffeine on blood pressure. Indeed, it is interesting to note that the intravenous administration of caffeine increases blood pressure even among regular coffee drinkers, while the consumption of the beverage itself has no impact. Overall, this data suggests that the neutral effect of coffee on blood pressure is due to the presence of molecules that reduce caffeine’s stimulation of the sympathetic nervous system. This is not surprising considering that coffee is not merely a source of caffeine, but rather a highly complex beverage containing more than a thousand distinct compounds, including several antioxidant and anti-inflammatory molecules.
Studies show that some of these molecules, such as chlorogenic acids and lignans, may also contribute to improving sugar metabolism and thus prevent type 2 diabetes. For example, an analysis of a dozen studies on the relationship between coffee consumption and the risk of type 2 diabetes shows that people who drank 4–6 cups a day were about 30% less likely to develop the disease compared to those who drank it very little or never. A prospective study involving 88,000 women aged 26 to 46 suggests that the protective effect of coffee may be even greater, and can be observed for smaller amounts of coffee, with a 13% and 42% reduction in risk for a daily consumption of 1 cup and 2–3 cups, respectively. These reductions are also observed for decaffeinated coffee, suggesting that, beyond caffeine, the molecules contained in this beverage can help maintain normal blood sugar levels.
Several recent studies also indicate that regular coffee consumption is associated with a decreased risk of neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease, several types of cancer, particularly liver cancer, a decreased risk of recurrence in people who have been affected by hormone-dependent breast and colon cancer, a decreased risk of end-stage renal disease, and a decreased risk of premature death. Coffee’s long-standing reputation as unhealthy is therefore irrelevant. While it is notably appreciated for its stimulating properties, coffee is a drink that has many positive effects, not only for preventing cardiovascular disease but also on health in general.