- A study of 400,000 middle-aged people (average age 51) shows that above-normal cholesterol levels are associated with a significant increase in the risk of cardiovascular disease in the decades that follow.
- This risk is particularly high in people who were under the age of 45 at the start of the study, suggesting that prolonged exposure to excess cholesterol plays a major role in increasing the risk of cardiovascular disease.
- Reducing cholesterol levels as early as possible, from early adulthood, through lifestyle changes (diet, exercise) can therefore limit the long-term exposure of blood vessels to atherogenic particles and thus reduce the cardiovascular events during aging.
It is now well established that high levels of cholesterol in the bloodstream promote the development of atherosclerosis and thereby increase the risk of cardiovascular events such as myocardial infarction and stroke. It is for this reason that the measurement of cholesterol has been part of the basic blood test for more than 30 years and that a deviation from normal values is generally considered a risk factor for cardiovascular disease.
Remember that cholesterol is insoluble in water and must be combined with lipoproteins to circulate in the blood. Routinely, the way to determine cholesterol levels is to measure all of these lipoproteins (what is called total cholesterol) and then distinguish two main types:
- HDL cholesterol, colloquially known as “good cholesterol” because it is involved in the elimination of cholesterol and therefore has a positive effect on cardiovascular health;
- LDL cholesterol, the “bad” cholesterol because of its involvement in the formation of atherosclerotic plaques that increase the risk of heart attack and stroke.
LDL cholesterol is difficult to measure directly and its concentration is rather calculated from the values determined for total cholesterol, HDL cholesterol and triglycerides using a mathematical formula:
[LDL cholesterol] = [Total cholesterol] – [HDL cholesterol] – [Triglycerides] / 2.2
However, this method has its limits, among other things because a large proportion of cholesterol can be transported by other types of lipoproteins and therefore does not appear in the calculation. However, it is very easy to measure all of these lipoproteins by simply subtracting HDL cholesterol from total cholesterol:
[Total cholesterol] – [HDL cholesterol] = [Non-HDL cholesterol]
This calculation makes it possible to obtain the concentration of what is called “non-HDL” cholesterol, i.e. all of the atherogenic lipoproteins [VLDL, IDL, LDL and Lp(a)] that are deposited at the level of the wall of the arteries and form atheromatous plaques that significantly increase the risk of cardiovascular problems. Although clinicians are more familiar with LDL cholesterol measurement, cardiology associations, including the Canadian Cardiovascular Society, now recommend that non-HDL cholesterol also be used as an alternative marker for risk assessment in adults.
The decision to initiate cholesterol-lowering therapy depends on the patient’s risk of experiencing a cardiovascular event in the next 10 years. To estimate this risk, clinicians use what is called a “risk score” (the Framingham risk score, for example), a calculation based primarily on the patient’s age, history of cardiovascular disease, family history and certain clinical values (blood pressure, blood sugar, cholesterol). For people who are at high risk of cardiovascular disease, especially those who have suffered a coronary event, there is no hesitation: all patients must be taken care of quickly, regardless of LDL or non-HDL cholesterol levels. Several clinical studies have shown that in this population, the main class of cholesterol-lowering drugs (statins) helps prevent recurrences and mortality, with an absolute risk reduction of around 4%. As a result, these drugs are now part of the standard therapeutic arsenal to treat anyone who has survived a coronary event or who has stable coronary heart disease.
The same goes for people with familial hypercholesterolemia (HF), a genetic disorder that exposes individuals to high levels of LDL cholesterol from birth and to a high risk for cardiovascular events before they even turn 40. A study has just recently shown that HF children who were treated with statins at an early age had a much lower incidence of cardiovascular events in adulthood (1% vs. 26%) than their parents who had not been treated early with statins.
However, the decision to treat high cholesterol is much more difficult for people who do not have these risk factors. Indeed, when the risk of cardiovascular events over the next 10 years is low or moderate, the guidelines tolerate much higher LDL and non-HDL cholesterol levels than in people at risk: for example, when we usually try to keep LDL cholesterol below 2 mmol/L for people at high risk, a threshold twice as high (5 mmol/L) is proposed before treating people at low risk (Table 1). In this population, there is therefore a great deal of room for maneuver in deciding whether or not to start pharmacological treatment or to fundamentally change lifestyle habits (diet, exercise) to normalize these cholesterol levels.
Table 1. Canadian Cardiovascular Society guidelines for dyslipidemia treatment thresholds. *FRS = Framingham Risk Score. Adapted from Anderson et al. (2016).
This decision is particularly difficult for young adults, who are generally considered to be at low risk of cardiovascular events over the next 10 years (age is one of the main factors used for risk assessment and therefore the younger you are, the lower the risk). On the one hand, a young person, say in their early forties, who has above-normal LDL or non-HDL cholesterol, but without exceeding the recommended thresholds and without presenting other risk factors, probably does not have a major risk of being affected by a short-term cardiovascular event. But given their young age, they may be exposed to this excess cholesterol for many years and their risk of cardiovascular disease may become higher than average once they turn 70 or 80.
Recent studies indicate that it would be wrong to overlook this long-term negative impact of higher-than-normal non-HDL cholesterol. For example, it has been shown that an increase in non-HDL cholesterol at a young age (before age 40) remains above normal for the following decades and increases the risk of cardiovascular disease by almost 4 times. Another study that followed for 25 years a young population (average age of 42 years) who presented a low risk of cardiovascular disease at 10 years (1.3%) obtained similar results: compared to people with normal non-HDL cholesterol (3.3 mmol/L), those with non-HDL cholesterol above 4 mmol/L had an 80% increased risk of cardiovascular mortality. As shown in Table 1, these non-HDL cholesterol values are below the thresholds considered to initiate treatment in people at low risk, suggesting that hypercholesterolemia that develops at a young age, even if it is mild and not threatening in the short term, may nevertheless have longer-term adverse effects.
This concept has just been confirmed by a very large study involving nearly 400,000 middle-aged people (average age 51) who were followed for a median period of 14 years (maximum 43 years). The results show a significant increase as a function of time in the risk of cardiovascular disease based on non-HDL cholesterol levels: compared to the low category (<2.6 mmol/L), the risk increases by almost 4 times for non-HDL cholesterol ≥ 5.7 mmol/L, as much in women (increase from 8% to 34%) as in men (increase from 13% to 44%) (Figure 1).
Figure 1. Increased incidence of cardiovascular disease based on non-HDL cholesterol levels. From Brunner et al. (2019).
The largest increase in risk associated with higher non-HDL cholesterol levels was observed in people who were under 45 years of age at the beginning of the study (risk ratio of 4.3 in women and 4.6 in men for non-HDL cholesterol ≥5.7 mmol/L vs. the reference value of 2.6 mmol/L) (Figure 2). In older people (60 years or more), these risk ratios are much lower (1.4 in women and 1.8 in men), confirming that it is prolonged exposure (for several decades) to high levels of non-HDL cholesterol that plays a major role in increasing the risk of cardiovascular disease.
Figure 2. Age-specific and sex-specific association of non-HDL cholesterol and cardiovascular disease. From Brunner et al. (2019).
According to the authors, there would therefore be great benefits in reducing non-HDL cholesterol levels as soon as possible to limit the long-term exposure of blood vessels to atherogenic particles and thus reduce the risk of cardiovascular events. An estimate based on the results obtained indicates that in people 45 years of age and under who have above-normal non-HDL cholesterol levels (3.7–4.8 mmol/L) and other risk factors (e.g. hypertension), a 50% reduction in this type of cholesterol would reduce the risk of cardiovascular disease at age 75 from 16% to 4% in women and from 29% to 6% in men. These significant reductions in long-term risk therefore add a new dimension to the prevention of cardiovascular disease: it is no longer only the presence of high cholesterol levels which must be considered, but also the duration of exposure to excess cholesterol.
What to do if your cholesterol is high
If your short-term risk of cardiovascular accident is high, for example, because you suffer from familial hypercholesterolemia or you combine several risk factors (heredity of early coronary artery disease, hypertension, diabetes, abdominal obesity), it is certain that your doctor will insist on prescribing a statin if your cholesterol is above normal.
For people who do not have these risk factors, the approach that is generally recommended is to modify lifestyle habits, particularly in terms of diet and physical activity. Several of these modifications have rapidly measurable impacts on non-HDL cholesterol levels: weight loss for obese or overweight people, replacing saturated fat with sources of monounsaturated fat (olive oil, for example) and omega-3 polyunsaturated fats (fatty fish, nuts and seeds), an increase in the consumption of soluble fibres, and the adoption of a regular physical activity program. This roughly corresponds to the Mediterranean diet, a diet that has repeatedly been associated with a decreased risk of several chronic diseases, particularly cardiovascular disease.
The advantage of adopting these lifestyle habits is that not only do they help normalize cholesterol levels, but they also have several other beneficial effects on cardiovascular health and health in general. Despite their well-documented clinical utility, randomized clinical studies indicate that statins fail to completely reduce the risk of cardiovascular events, both in primary and secondary prevention. This is not surprising, since atherosclerosis is a multifactorial disease, which involves several phenomena other than cholesterol (chronic inflammation in particular). This complexity means that no single drug can prevent cardiovascular disease alone. And it is only by adopting a comprehensive approach based on a healthy lifestyle that we can make significant progress in preventing these diseases.
The role of dietary fat in the development of obesity, cardiovascular disease and type 2 diabetes has been the subject of vigorous scientific debate for several years. In an article recently published in the prestigious Science, four experts on dietary fat and carbohydrate with very different perspectives on the issue (David Ludwig, Jeff Volek, Walter Willett, and Marian Neuhouser) identified 5 basic principles widely accepted in the scientific community and that can be of great help for non-specialists trying to navigate this issue.
This summary is important as the public is constantly bombarded with contradictory claims about the benefits and harmful effects of dietary fat. Two great, but diametrically opposed currents have emerged over the last few decades:
- The classic low-fat position, i.e., reducing fat intake, adopted since the 1980s by most governments and medical organizations. This approach is based on the fact that fats are twice as caloric as carbohydrates (and therefore more obesigenic) and that saturated fats increase LDL cholesterol levels, a major risk factor for cardiovascular disease. As a result, the main goal of healthy eating should be to reduce the total fat intake (especially saturated fat) and replace it with carbohydrate sources (vegetables, bread, cereals, rice and pasta). An argument in favour of this type of diet is that many cultures that have a low-fat diet (Okinawa’s inhabitants, for example) have exceptional longevity.
- The low-carb position, currently very popular as evidenced by the ketogenic diet, advocates exactly the opposite, i.e., reducing carbohydrate intake and increasing fat intake. This approach is based on several observations showing that increased carbohydrate consumption in recent years coincides with a phenomenal increase in the incidence of obesity in North America, suggesting that it is sugars and not fats that are responsible for excess weight and the resulting chronic diseases (cardiovascular disease, type 2 diabetes, some cancers). One argument in favour of this position is that an increase in insulin in response to carbohydrate consumption can actually promote fat accumulation and that low-carb diets are generally more effective at promoting weight loss, at least in the short term.
Reaching a consensus from two such extreme positions is not easy! Nevertheless, when we look at different forms of carbohydrates and fat in our diet, the reality is much more nuanced, and it becomes possible to see that a number of points are common to both approaches. By critically analyzing the data currently available, the authors have managed to identify at least five major principles they all agree on:
1) Eating unprocessed foods of good nutritional quality helps to stay healthy without having to worry about the amount of fat or carbohydrate consumed.
A common point of the low-fat and low-carb approaches is that each one is convinced it represents the optimal diet for health. In fact, a simple observation of food traditions around the world shows that there are several food combinations that allow you to live longer and be healthy. For example, Japan, France and Israel are the industrialized countries with the two lowest mortality rates from cardiovascular disease (110, 126 and 132 deaths per 100,000, respectively) despite considerable differences in the proportion of carbohydrates and fat from their diet.
It is the massive influx of ultra-processed industrial foods high in fat, sugar and salt that is the major cause of the obesity epidemic currently affecting the world’s population. All countries, without exception, that have shifted their traditional consumption of natural foods to processed foods have seen the incidence of obesity, type 2 diabetes, and cardiovascular disease affecting their population increase dramatically. The first step in combating diet-related chronic diseases is therefore not so much to count the amount of carbohydrate or fat consumed, but rather to eat “real” unprocessed foods. The best way to do this is simply to focus on plant-based foods such as fruits, vegetables, legumes and whole-grain cereals, while reducing those of animal origin and minimizing processed industrial foods such as deli meats, sugary drinks, and other junk food products.
2) Replace saturated fat with unsaturated fat.
The Seven Countries Study showed that the incidence of cardiovascular disease was closely correlated with saturated fat intake (mainly found in foods of animal origin such as meats and dairy products). A large number of studies have shown that replacing these saturated fats with unsaturated fats (e.g., vegetable oils) is associated with a significant reduction in the risk of cardiovascular events and premature mortality. A reduction in saturated fat intake, combined with an increased intake of high quality unsaturated fat (particularly monounsaturated and omega-3 polyunsaturated), is the optimal combination to prevent cardiovascular disease and reduce the risk of premature mortality.
These benefits can be explained by the many negative effects of an excess of saturated fat on health. In addition to increasing LDL cholesterol levels, an important risk factor for cardiovascular disease, a high intake of saturated fat causes an increase in the production of inflammatory molecules, an alteration of the function of the mitochondria (the power plants of the cell), and a disturbance of the normal composition of the intestinal microbiome. Not to mention that the organoleptic properties of a diet rich in saturated fats reduce the feeling of satiety and encourage overconsumption of food and accumulation of excess fat, a major risk factor for cardiovascular disease, type 2 diabetes and some cancers.
3) Replace refined carbohydrates with complex carbohydrates.
The big mistake of the “anti-fat crusade” of the ’80s and ’90s was to believe that any carbohydrate source, even the sugars found in processed industrial foods (refined flours, added sugars), was preferable to saturated fats. This belief was unjustified, as subsequent studies have demonstrated beyond a doubt that these refined sugars promote atherosclerosis and can even triple the risk of cardiovascular mortality when consumed in large quantities. In other words, any benefit that can come from reducing saturated fat intake is immediately countered by the negative effect of refined sugars on the cardiovascular system. On the other hand, when saturated fats are replaced by complex carbohydrates (whole grains, for example), there is actually a significant decrease in the risk of cardiovascular events.
Another reason to avoid foods containing refined or added sugars is that they have low nutritional value and cause significant variations in blood glucose and insulin secretion. These metabolic disturbances promote excess weight and the development of insulin resistance and dyslipidemia, conditions that significantly increase the risk of cardiovascular events. Conversely, increased intake of complex carbohydrates in whole-grain cereals, legumes, and other vegetables helps keep blood glucose and insulin levels stable. In addition, unrefined plant foods represent an exceptional source of vitamins, minerals and antioxidant phytochemicals essential for maintaining health. Their high fibre content also allows the establishment of a diverse intestinal microbiome, whose fermentation activity generates short-chain fatty acids with anti-inflammatory and anticancer properties.
4) A high-fat low-carb diet may be beneficial for people who have disorders of carbohydrate metabolism.
In recent years, research has shown that people who have normal sugar metabolism may tolerate a higher proportion of carbohydrates, while those with glucose intolerance or insulin resistance may benefit from adopting a low-carb diet richer in fat. This seems particularly true for people with diabetes and prediabetes. For example, an Italian study of people with type 2 diabetes showed that a diet high in monounsaturated fat (42% of total calories) was more effective in reducing the accumulation of fat in the liver (a major contributor to the development of type 2 diabetes) than a diet low in fat (28% of total calories).
These benefits seem even more pronounced for the ketogenic diet, in which the consumption of carbohydrates is reduced to a minimum (<50 g per day). Studies show that in people with a metabolic syndrome, this type of diet can generate a fat loss (total and abdominal) greater than a hypocaloric diet low in fat, as well as a higher reduction of blood triglycerides and several markers of inflammation. In people with type 2 diabetes, a recent study shows that in the majority of patients, the ketogenic diet is able to reduce the levels of glycated haemoglobin (a marker of chronic hyperglycaemia) to a normal level, and this without drugs other than metformin. Even people with type 1 diabetes can benefit considerably from a ketogenic diet: a study of 316 children and adults with this disease shows that the adoption of a ketogenic diet allows an exceptional control of glycemia and the maintenance of excellent metabolic health over a 2-year period.
5) A low-carb or ketogenic diet does not require a high intake of proteins and fats of animal origin.
Several forms of low carbohydrate or ketogenic diets recommend a high intake of animal foods (butter, meat, charcuteries, etc.) high in saturated fats. As mentioned above, these saturated fats have several negative effects (increase of LDL, inflammation, etc.), and one can therefore question the long-term impact of this type of low-carb diet on the risk of cardiovascular disease. Moreover, a study recently published in The Lancet indicates that people who consume little carbohydrates (<40% of calories), but a lot of fat and protein of animal origin, have a significantly increased risk of premature death. For those wishing to adopt a ketogenic diet, it is therefore important to realize that it is quite possible to reduce the proportion of carbohydrates in the diet by substituting cereals and other carbohydrate sources with foods rich in unsaturated fats like vegetable oils, vegetables rich in fat (nuts, seeds, avocado, olives) as well as fatty fish.
In short, the current debate about the merits of low-fat and low-carb diets is not really relevant: for the vast majority of the population, several combinations of fat and carbohydrate make it possible to remain in good health and at low risk of chronic diseases, provided that these fats and carbohydrates come from foods of good nutritional quality. It is the overconsumption of ultra-processed foods, high in fat and refined sugars, which is responsible for the dramatic rise in food-related diseases, particularly obesity and type 2 diabetes. Restricting the consumption of these industrial foods and replacing them with “natural” foods, especially those of plant origin, remains the best way to reduce the risk of developing these diseases. On the other hand, for overweight individuals with metabolic syndrome or type 2 diabetes, currently available scientific evidence suggests that a reduction in carbohydrate intake by adopting low-carb and ketogenic diets could be beneficial.
Updated on January 24, 2019
It is well established that aspirin is beneficial in secondary prevention, that is, for patients who have already suffered a myocardial infarction or stroke or who have a condition such as angina, acute coronary syndrome, or myocardial ischemia, and for those who have undergone coronary artery bypass grafting or coronary angioplasty. It has been suggested that aspirin may also be beneficial in primary prevention, i.e., to prevent cardiovascular events in those who have never had one, but are at risk. For the last few decades, aspirin has been used at low doses to prevent myocardial infarction and stroke; however, a recent study indicates that this drug does not prevent a first heart attack or stroke in people with moderate cardiovascular risk. In another study, this time of people with type 2 diabetes, taking aspirin modestly reduced the risk of cardiovascular events, but increased the risk of serious bleeding.
Primary prevention in people at moderate risk
Low-dose aspirin (100 mg/day) does not prevent a first heart attack or stroke in people at moderate risk of developing cardiovascular disease according to the ARRIVE study (Aspirin to Reduce Risk of Initial Vascular Events), published in The Lancet in August 2018. Aspirin has been tested in primary prevention over an average of 5 years, with 12,546 people living in the United Kingdom, Poland, Germany, Italy, Ireland, Spain and the USA. During these years, participants who took 100 mg of aspirin daily did not have significantly fewer vascular events than those who took a placebo [269 participants (4.3%) vs. 281 (4.5%); p=0.6038]. There were fewer vascular events than expected in this study, suggesting that participants had low cardiovascular risk rather than moderate risk. Gastrointestinal bleeding, which was mostly mild, was significantly higher in the aspirin group than in the placebo group [61 participants (0.97%) vs. 29 (0.46%); p=0007].
The authors of the ARRIVE study conclude that “The use of aspirin remains a decision that should involve a thoughtful discussion between a clinician and a patient, given the need to weigh cardiovascular and possible cancer prevention benefits against the bleeding risks, patient preferences, cost, and other factors. The ARRIVE data must be interpreted and used in the context of other studies, which have tended to show a reduction primarily in myocardial infarction, with less of an effect on total stroke (including both ischaemic and haemorrhagic stroke).”
Primary prevention in people with diabetes
Aspirin has been tested for primary prevention in 15,480 people with type 2 diabetes, who are therefore at increased risk of developing or dying from cardiovascular disease. During the seven years of the randomized study, people who took 100 mg of aspirin daily had significantly fewer serious vascular events than those who took a placebo [658 participants (8.5%) vs. 743 (9.6%)]. In contrast, major bleeding was greater in the aspirin group than in the placebo group [314 participants (4.1%) vs. 245 (3.2%)]. There was no significant difference between the group that took aspirin and the placebo group for gastrointestinal cancer incidence [157 participants (2.0%) vs. 158 (2.0%)] or any type of cancer [897 participants (11.6%) vs. 887 (11.5%)]. The authors of this study conclude that the benefits of aspirin for people with diabetes are largely outweighed by the risk of bleeding.
Aspirin for prevention in the elderly
The effects of daily low-dose aspirin were evaluated specifically in the elderly in the ASPREE study (Aspirin in Reducing Events in the Elderly), the results of which were published as three articles in the New England Journal Of Medicine (see here, here, and here). The study enlisted 19,114 Australians and Americans aged 70 or older who did not have cardiovascular disease, dementia, or physical disability. Participants were randomly assigned to take a 100 mg enteric-coated aspirin or placebo tablet daily for 5 years. The primary endpoint was a composite endpoint including death, dementia, and persistent physical disability. Secondary endpoints included severe bleeding and cardiovascular disease (nonfatal myocardial infarction, fatal coronary heart disease, fatal or nonfatal stroke, hospitalization for heart failure).
Aspirin did not prolong disability-free survival in the elderly and did not decrease the risk of cardiovascular disease, but it increased the rate of serious bleeding compared with placebo. The composite rate of mortality, dementia, and persistent physical disability was 21.5 and 21.2 events per 1,000 person-years in the group who took aspirin and in the placebo group, respectively. The rates of cardiovascular events were 10.7 and 11.3 events per 1,000 person-years in the aspirin group and the placebo group, respectively. The rate of serious bleeding was significantly higher (P <0.001) in the aspirin group (8.6 events per 1,000 person-years) than in the placebo group (6.2 events per 1,000 person-years). Finally, the all-cause mortality rate was higher in the aspirin group than in the placebo group, a result mainly attributable to deaths from cancer. Since an increase in mortality has not been observed in previous studies on aspirin used for prevention, this unexpected result should be interpreted with caution according to the authors.
Systematic review and meta-analysis
A synthesis of 13 randomized controlled trials of aspirin for primary prevention of cardiovascular disease, including the 3 major trials in 2018, was published in January 2019 in JAMA. All studies included 164,225 participants aged 53 to 74 and a follow-up of 1,050,511 person-years. This meta-analysis confirms that aspirin is associated with a decreased risk of cardiovascular events (cardiovascular mortality, nonfatal myocardial infarction, nonfatal stroke) and an increased risk of major bleeding. Aspirin was associated with an 11% reduction in relative risk (absolute risk reduction of 0.38%) of cardiovascular events and a 43% greater relative risk of major bleeding (absolute risk increase of 0.47%). As a result, 265 people will need to be treated with aspirin for 5 years to prevent a cardiovascular event, but one in 210 treated people will experience major bleeding. Because of the unfavourable benefit-to-disadvantage ratio, the European guidelines do not recommend taking aspirin until cardiovascular disease occurs (secondary prevention), i.e., at a time when the benefits outweigh the risks of adverse effects. On the other hand, the US Preventive Services Task Force (USPSTF) recommends improving the benefit-harm ratio for aspirin in primary prevention by estimating the risks of cardiovascular events and bleeding for each patient, considering the potential longer-term benefits of aspirin for the prevention of colorectal cancer, and carefully discussing with patients the balance between the risks of vascular and haemorrhagic events.
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 [-0.21 mmol/L on average], systolic blood pressure [-2.72 mmHg on average], fasting glucose concentration [-0.10 mmol/L on average], body mass index [-0.36 kg/m2on average], glycated haemoglobin [HbA1c, -0.20% on average], and tumour necrosis factor alpha [TNF-alpha, 0.99 pg/mL on average], 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 [RCTs] 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.
Updated on February 11, 2019
Not only are plants important sources of vitamins, fibres and minerals but they also contain phytochemicals such as polyphenols that play a very important role in the positive effects of these foods on cardiovascular health. Among the thousands of distinct polyphenols found in nature, the family of flavonoids has received special attention in recent years because of its presence in a large number of plants (fruits, vegetables, nuts, legumes) and beverages (tea, coffee, red wine) that are part of our daily diet. The impact of these molecules on health appears to be particularly important, as population studies indicate that people with the highest flavonoid intake have a lower risk of stroke or coronary artery disease, effects that are accompanied by a decrease in cardiovascular mortality and overall mortality.
Cocoa and its by-products, especially dark chocolate, are exceptional sources of polyphenols (Table 1), in particular flavonoids, suggesting that regular consumption of cocoa products could be very positive for cardiovascular health.
Table 1. Polyphenol content of some foods and beverages. Adapted from Pérez-Jiménez et al. (2010).
(mg/100 g or 100 mL)
The first clue to this positive effect comes from Marjorie McCullough’s observations on the Kuna Indians of the San Blass Islands, an archipelago off Panama. These people are very large consumers of cocoa, which they use to prepare a beverage according to the traditional method of pre-Colombian civilizations. The Kuna drink about five cups of cocoa a day, which translates into a polyphenol intake of around 1800 mg per day, almost 10 times more than North Americans. These people are also distinguished for their very low blood pressure (110/70 mmHg even at over 60 years old), despite a very high salt diet, and their low incidence of myocardial infarction and stroke. These characteristics are not of genetic origin, because the individuals who have left the island to live on the mainland see their blood pressure quickly increase. Among the lifestyle factors that may explain this difference, the most plausible is the drastic decrease in continental cocoa consumption, which is 10 times lower than among islanders. Therefore, it seems that cocoa polyphenols can have a real impact on cardiovascular health by lowering blood pressure and, at the same time, the risk of ischemic events such as heart attack or stroke that result from hypertension.
Several epidemiological studies have confirmed that high cocoa intake is indeed associated with a decrease in blood pressure and a reduction in the risk of cardiovascular disease and premature mortality. For example, a 15-year Dutch study of 500 people over the age of 65 found that those who consumed the most cocoa-based products had an average systolic pressure of 3.7 mm Hg and a marked reduction (50%) in the risk of cardiovascular mortality. These results have been confirmed by several randomized clinical trials where the consumption of dark chocolate, cocoa or cocoa-derived polyphenols is associated with a decrease in blood pressure and an improvement in endothelial function and insulin sensitivity. These vascular effects are largely due to an increase in the formation of nitric oxide (NO), a powerful vasodilator, by some cocoa flavonoids. A beneficial effect of cocoa consumption on the lipid profile (triglycerides, LDL and HDL cholesterol) and on the reduction of chronic inflammation has also been reported and could contribute to the benefits of dark chocolate for cardiovascular health.
These beneficial effects are also suggested by the results of a meta-analysis of 14 prospective studies conducted with a total of 508,705 participants, followed for a period of 5 to 16 years. The authors observed that people who consumed the most cocoa had a lower risk of coronary heart disease (10% decrease), stroke (16% decrease), and diabetes (18% decrease).
The most recent meta-analysis, which included 23 prospective studies with 405,304 participants, indicates that chocolate consumption is associated with a reduced risk of cardiovascular disease (CVD), if consumption is limited to less than 100 g/week. Those who consumed more chocolate had a 12% lower risk of CVD in general (stroke: -16.3%, myocardial infarction: -16.2%) than those who consumed little. However, the dose-response analysis (Figure 1) shows that at more than 100 g/week there is no longer any protective effect and that the risk of CVD increases at higher doses, which could be attributable to the harmful effect of consuming too much sugar. According to the authors of this meta-analysis, the best dose of chocolate to reduce the risk of CVD is 45 g/week (about half of a 100 g chocolate bar, a common size sold in grocery stores).
Figure 1. Dose-effect association between the consumption of chocolate and the risks of cardiovascular events. From Ren et al., Heart, 2019.
It is now clearly established that several risk factors for cardiovascular disease (hypertension, inflammation, insulin resistance, metabolic syndrome) also increase the risk of cognitive decline and dementia. Conversely, recognized factors to protect cardiovascular health, such as physical exercise or the Mediterranean diet, are associated with a significant decrease in the risk of cognitive disorders. In other words, what is good for the heart is also good for the brain, which raises the interesting possibility that the regular consumption of cocoa-based products can also result in benefits for cognitive function. Studies conducted to date support this, as a high intake of flavonoid-rich foods such as tea, red wine and chocolate is associated with reduced risk of cognitive decline and improved brain performance. In a study of people aged 65 to 82 who showed clinical signs of early cognitive decline, daily consumption of a beverage made with chocolate high in polyphenols was associated with significant improvement of cognitive functions.
More recently, a randomized clinical study showed that dark chocolate consumption was associated with a significant improvement in visual acuity and contrast sensitivity a few hours after intake, a positive impact possibly related to an improvement in blood circulation in the richly vascularized retina. Milk chocolate, which contains less polyphenols, has no effect, suggesting that flavonoids in cocoa are responsible for this improvement in vision.