Choosing dietary sources of unsaturated fats has many health benefits

Choosing dietary sources of unsaturated fats has many health benefits

OVERVIEW

  • Unsaturated fatty acids, found mainly in vegetable oils, nuts, certain seeds and fatty fish, play several essential roles for the proper functioning of the human body.
  • While saturated fatty acids, found mainly in foods of animal origin, increase LDL cholesterol levels, unsaturated fats lower this type of cholesterol and thereby reduce the risk of cardiovascular events.
  • Current scientific consensus is therefore that a reduction in saturated fat intake combined with an increased intake of unsaturated fat represents the optimal combination of fat to prevent cardiovascular disease and reduce the risk of premature mortality.
Most nutrition experts now agree that a reduction in saturated fat intake combined with an increased intake of quality unsaturated fat (especially monounsaturated and polyunsaturated omega-3) represents the optimal combination of fat to prevent cardiovascular disease and reduce the risk of premature death. The current consensus, recently summarized in articles published in the journals Science and BMJ, is therefore to choose dietary sources of unsaturated fats, such as vegetable oils (particularly extra virgin olive oil and those rich in omega-3s such as canola), nuts, certain seeds (flax, chia, hemp) and fatty fish (salmon, sardine), while limiting the intake of foods mainly composed of saturated fats such as red meat. This roughly corresponds to the Mediterranean diet, a way of eating that has repeatedly been associated with a decreased risk of several chronic diseases, especially cardiovascular disease.

Yet despite this scientific consensus, the popular press and social media are full of conflicting information about the impact of different forms of dietary fat on health. This has become particularly striking since the rise in popularity of low-carbohydrate (low-carb) diets, notably the ketogenic diet, which advocates a drastic reduction in carbohydrates combined with a high fat intake. In general, these diets make no distinction as to the type of fat that should be consumed, which can lead to questionable recommendations like adding butter to your coffee or eating bacon every day. As a result, followers of these diets may eat excessive amounts of foods high in saturated fat, and studies show that this type of diet is associated with a significant increase in LDL cholesterol, an important risk factor for cardiovascular disease. According to a recent study, a low-carbohydrate diet (<40% of calories), but that contains a lot of fat and protein of animal origin, could even significantly increase the risk of premature death.

As a result, there is a lot of confusion surrounding the effects of different dietary fats on health. To get a clearer picture, it seems useful to take a look at the main differences between saturated and unsaturated fats, both in terms of their chemical structure and their effects on the development of certain diseases.

A little chemistry…
Fatty acids are carbon chains of variable length whose rigidity varies depending on the degree of saturation of these carbon atoms by hydrogen atoms. When all the carbon atoms in the chain form single bonds with each other by engaging two electrons (one from each carbon), the fatty acid is said to be saturated because each carbon carries as much hydrogen as possible. Conversely, when certain carbons in the chain use 4 electrons to form a double bond between them (2 from each carbon), the fatty acid is said to be unsaturated because it lacks hydrogen atoms.

These differences in saturation have a great influence on the physicochemical properties of fatty acids. When saturated, fatty acids are linear chains that allow molecules to squeeze tightly against each other and thus be more stable. It is for this reason that butter and animal fats, rich sources of these saturated fats, are solid or semi-solid at room temperature and require a source of heat to melt.

Unsaturated fatty acids have a very different structure (Figure 1). The double bonds in their chains create points of stiffness that produce a “crease” in the chain and prevent molecules from tightening against each other as closely as saturated fat. Foods that are mainly composed of unsaturated fats, vegetable oils for example, are therefore liquid at room temperature. This fluidity directly depends on the number of double bonds present in the chain of unsaturated fat: monounsaturated fats contain only one double bond and are therefore less fluid than polyunsaturated fats which contain 2 or 3, and this is why olive oil, a rich source of monounsaturated fat, is liquid at room temperature but solidifies in the refrigerator, while oils rich in polyunsaturated fat remain liquid even at cold temperatures.

Figure 1. Structure of the main types of saturated, monounsaturated and polyunsaturated omega-3 and omega-6 fats. The main food sources for each fat are shown in italics.

Polyunsaturated fats can be classified into two main classes, omega-3 and omega-6. The term omega refers to the locationof the first double bond in the fatty acid chain from its end (omega is the last letter of the Greek alphabet). An omega-3 or omega-6 polyunsaturated fatty acid is therefore a fat whose first double bond is located in position 3 or 6, respectively (indicated in red in the figure).

It should be noted that there is no food that contains only one type of fat. On the other hand, plant foods (especially oils, seeds and nuts) are generally made up of unsaturated fats, while those of animal origin, such as meat, eggs and dairy products, contain more saturated fat. There are, however, exceptions: some tropical oils like palm and coconut oils contain large amounts of saturated fat (more than butter), while some meats like fatty fish are rich sources of omega-3 polyunsaturated fats such as eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids.

Physiological roles of fatty acids
All fatty acids, whether saturated or unsaturated, play important roles in the normal functioning of the human body, especially as constituents of cell membranes and as a source of energy for our cells. From a dietary point of view, however, only polyunsaturated fats are essential: while our metabolism is capable of producing saturated and monounsaturated fatty acids on its own (mainly from glucose and fructose in the liver), linoleic (omega-6) and linolenic (omega-3) acids must absolutely be obtained from food. These two polyunsaturated fats, as well as their longer chain derivatives (ALA, EPA, DHA), play essential roles in several basic physiological functions, in particular in the brain, retina, heart, and reproductive and immune systems. These benefits are largely due to the degree of unsaturation of these fats, which gives greater fluidity to cell membranes, and at the same time facilitate a host of processes such as the transmission of electrical impulses in the heart or neurotransmitters in the synapses of the brain. In short, while all fats have important functions for the functioning of the body, polyunsaturated fats clearly stand out for their contribution to several processes essential to life.

Impacts on cholesterol
Another major difference between saturated and unsaturated fatty acids is their respective effects on LDL cholesterol levels. After absorption in the intestine, the fats ingested during the meal (mainly in the form of triglycerides and cholesterol) are “packaged” in structures called chylomicrons and transported to the peripheral organs (the fatty tissue and the muscles, mainly) where they are captured and used as a source of energy or stored for future use. The residues of these chylomicrons, containing the portion of excess fatty acids and cholesterol, are then transported to the liver, where they are taken up and will influence certain genes involved in the production of low-density lipoproteins (LDL), which serve to transport cholesterol, as well as their receptors (LDLR), which serve to eliminate it from the blood circulation.

And this is where the main difference between saturated and unsaturated fats lies: a very large number of studies have shown that saturated fats (especially those made up of 12, 14 and 16 carbon atoms) increase LDL production while decreasing that of its receptor, with the result that the amount of LDL cholesterol in the blood increases. Conversely, while polyunsaturated fats also increase LDL cholesterol production, they also increase the number and efficiency of LDLR receptors, which overall lowers LDL cholesterol levels in the blood. It has been proposed that this greater activity of the LDLR receptor is due to an increase in the fluidity of the membranes caused by the presence of polyunsaturated fats which would allow the receptor to recycle more quickly on the surface liver cells (and therefore be able to carry more LDL particles inside the cells).

Reduction of the risk of cardiovascular disease
A very large number of epidemiological studies have shown that an increase in LDL cholesterol levels is associated with an increased risk of cardiovascular diseases. Since saturated fat increases LDL cholesterol while unsaturated fat decreases it, we can expect that replacing saturated fat with unsaturated fat will lower the risk of these diseases. And that is exactly what studies show: for example, an analysis of 11 prospective studies indicates that replacing 5% of caloric intake from saturated fat with polyunsaturated fat was associated with a 13% decrease in the risk of coronary artery disease. A similar decrease has been observed in clinical studies, where replacing every 1% of energy from saturated fat with unsaturated fat reduced the risk of cardiovascular events by 2%. In light of these results, there is no doubt that substituting saturated fats with unsaturated fats is an essential dietary change to reduce the risk of cardiovascular disease.

A very important point of these studies, which is still poorly understood by many people (including some health professionals), is that it is not only a reduction of saturated fat intake that counts for improving the health of the heart and vessels, but most importantly the source of energy that is consumed to replace these saturated fats. For example, while the substitution of saturated fats by polyunsaturated fats, monounsaturated fats or sources of complex carbohydrates like whole grains is associated with a substantial reduction in the risk of cardiovascular disease, this decrease is completely abolished when saturated fats are replaced by trans fats or poor quality carbohydrate sources (e.g., refined flours and added sugars) (Figure 2). Clinical studies indicate that the negative effect of an increased intake of simple sugars is caused by a reduction in HDL cholesterol (the good one) as well as an increase in triglyceride levels. In other words, if a person decreases their intake of saturated fat while simultaneously increasing their consumption of simple carbohydrates (white bread, potatoes, processed foods containing added sugars), these sugars simply cancel any potential cardiovascular benefit from reducing saturated fat intake.


Figure 2. Modulation of the risk of coronary heart disease following a substitution of saturated fat by unsaturated fat or by different sources of carbohydrates. The values shown correspond to variations in the risk of coronary heart disease following a replacement of 5% of the caloric intake from saturated fat by 5% of the various energy sources. Adapted from Li et al. (2015).

Another implication of these results is that one should be wary of “low-fat” or “0% fat” products, even though these foods are generally promoted as healthier. In the vast majority of cases, reducing saturated fat in these products involves the parallel addition of simple sugars, which counteracts the positive effects of reducing saturated fat.

This increased risk from simple sugars largely explains the confusion generated by some studies suggesting that there is no link between the consumption of saturated fat and the risk of cardiovascular disease (see here and here, for example). However, most participants in these studies used simple carbohydrates as an energy source to replace saturated fat, which outweighed the benefits of reduced intake of saturated fat. Unfortunately, media coverage of these studies did not capture these nuances, with the result that many people may have mistakenly believed that a high intake of saturated fat posed no risk to cardiovascular health.

In conclusion, it is worth recalling once again the current scientific consensus, stated following the critical examination of several hundred studies: replacing saturated fats by unsaturated fats (monounsaturated or polyunsaturated) is associated with a significant reduction in the risk of cardiovascular disease. As mentioned earlier, the easiest way to make this substitution is to use vegetable oils as the main fatty substance instead of butter and to choose foods rich in unsaturated fats such as nuts, certain seeds and fatty fish (salmon, sardine), while limiting the intake of foods rich in saturated fats such as red meat. It is also interesting to note that in addition to exerting positive effects on the cardiovascular system, recent studies suggest that this type of diet prevents excessive accumulation of fat in the liver (liver steatosis), an important risk factor of insulin resistance and therefore type 2 diabetes. An important role in liver function is also suggested by the recent observation that replacing saturated fats of animal origin by mono- or polyunsaturated fats was associated with a significant reduction in the risk of hepatocellular carcinoma, the main form of liver cancer. Consequently, there are only advantages to choosing dietary sources of unsaturated fat.

Spicing up the prevention of cardiovascular disease with chili peppers

Spicing up the prevention of cardiovascular disease with chili peppers

OVERVIEW

  • The frequency of weekly consumption of chili peppers by 22,811 Italians from the Molise region was measured over an 8-year period.
  • At the same time, researchers identified deaths from cardiovascular disease, cancer or other causes that occurred during this period.
  • Results show that people who eat chilies 4 or more times per week have a 44% and 61% reduced risk of death from myocardial infarction or stroke, respectively, compared to those who never or very rarely eat them.

Chili peppers (Capsicum spp.) are native to South America, where they were already being cultivated for culinary purposes more than 6,000 years ago. Following the discovery of America by Europeans in the 15th century, these hot peppers were disseminated worldwide by Portuguese sailors (particularly in India and Asia), where they were quickly adopted and became essential ingredients in the culinary cultures of these countries.

The gastronomic value of chilies obviously comes from their spicy flavour, which distinctively enhances the taste of different dishes. This property is due to the presence of capsaicin (Figure 1), a phenolic compound that specifically interacts with certain receptors (TRPV1 for Transient Receptor Potential Vanilloid) involved in the pain signal generated by temperatures above 43ºC.

Figure 1. Molecular structure of capsaicin, the molecule responsible for the spicy taste of chili peppers.

By binding to the TRPV1 receptor present in the mouth, capsaicin therefore causes a feeling of heat or a burning sensation, which completely tricks the brain into believing that the mouth is literally “on fire”. The reason many people are attracted to these “painful” substances is still not understood, but could be related to the release of pleasure molecules (endorphins) to mitigate the effects of the “burn” detected by the brain.

In addition to their unique taste properties, a recent study suggests that chili peppers may have positive health effects, particularly for cardiovascular disease. Over an 8-year period, researchers followed just over 20,000 people recruited into the Moli-sani Project, a prospective study of residents of the Molise region of southeastern Italy. By analyzing deaths during this period according to the frequency of chili pepper consumption by participants, the researchers found that the risk of dying prematurely from all causes was reduced by 23% for hot pepper lovers (consumption 4 times per week). This decrease was particularly apparent for mortality linked to coronary heart disease (44%) and cerebrovascular disease (61%) (Figure 2). A downward trend was observed for cancer mortality, but the difference is not statistically significant.

Figure 2. Reduced risk of all-cause mortality and mortality related to various diseases among regular chili pepper consumers. Adapted from Bonaccio et al. (2019). N.S., not significant.

These observations are in agreement with previous studies that have observed a significant reduction (approximately 10–20%) of premature mortality among the largest consumers of spicy foods (here and here, for example).

As the editorial accompanying the article points out, although this type of population study does not directly establish a causal link between chili pepper consumption and mortality, it remains that the experimental data accumulated in recent years make this link biologically plausible. On the one hand, several studies have suggested that capsaicin may help prevent the development of obesity, an important risk factor for diabetes and cardiovascular disease. For example, epidemiological studies have observed that regular consumption of these peppers is associated with a reduction in the prevalence of obesity in certain populations, and clinical studies have observed a loss of abdominal fat following the administration of a supplement of capsinoids (capsaicin and related molecules) compared to placebo. This positive effect of capsaicin on body weight maintenance is mainly linked to a decrease in calorie intake, caused by decreased appetite and increased satiety.

On the other hand, it should be noted that capsaicin also influences other phenomena linked to an increased risk of cardiovascular disease, notably by improving the response to insulin, reducing the oxidation of low-density lipoproteins (LDL), and improving endothelial function. Studies have also suggested that people who season their food with hot peppers eat less salt and are less at risk for hypertension, the main risk factor for cardiovascular events.

Overall, these observations raise the interesting possibility that some minor dietary changes, such as the addition of chili peppers, may have positive impacts on health, particularly at the cardiovascular level. Of course, there should be no illusions: if a person’s diet is based on ultra-processed foods and contains very little fruit and vegetables, it is not by adding sriracha sauce or Tabasco that they will manage to decrease their risk of cardiovascular disease. But in the context of a diet known to be positive for the health of the heart and vessels, such as the Mediterranean diet (adopted by most of the participants of the study mentioned above), it is possible that the positive biological effects of chili peppers on body weight, blood sugar and reduced salt intake may accentuate the benefits associated with this diet and therefore have a positive impact on health.

Toward a consensus on the effects of dietary fat on health

Toward a consensus on the effects of dietary fat on health

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.

The effects of berries on cardiovascular health

The effects of berries on cardiovascular health

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 compoundsFlavonoidsAnthocyanins
(mg/100 g fresh fruit)(mg/100 g fresh fruit)(mg/100 g fresh fruit)
Raspberry (Rubus ideaous)121699
Blackberry (Rubus fruticosus)48627682–326
Strawberry (Fragaria x. ananassa)31354
Blueberry (Vaccinium corymbosum)261–5855025–495
Bilberry (Vaccinium myrtillus )52544300
Cranberry (Vaccinium macrocarpon)31515767–140
Redcurrant (Ribes rubrum)1400922
Blackcurrant (Ribes nigrum)29-604644
Elderberry (Sambucus nigra)1044245-791
Red cranberry (Vitis vitis-idea)6527477

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.

Population studies
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.

The effects of nitrates and nitrites on the cardiovascular system

The effects of nitrates and nitrites on the cardiovascular system

Updated May 23, 2018

Nitrates (NO3) and nitrites (NO2) are mostly known to the public as undesirable residues of the agri-food chain as they are associated with potentially carcinogenic effects. Yet, these molecules are naturally found in fruits and vegetables (nitrates) as well as in the human body (nitrates and nitrites) where they contribute to important physiological functions, particularly in the cardiovascular system. Moreover, it has now been proven that dietary nitrates can be beneficial to cardiovascular health and sports performance, as will be discussed below.

Nitrates and Nitrites: Dangerous or Harmless?

During the curing process used to transform meats into charcuterie (ham, sausages, bacon, etc.), nitrite salt is added to stabilize the colour and taste of meats and to prevent the development of pathogenic microorganisms. Nitrite salt is in fact very effective in preventing the proliferation of bacteria, including the formidable Clostridium botulinum, which produces a powerful toxin that causes botulism, a very serious, sometimes deadly, paralytic illness. Nitrates and nitrites themselves are not carcinogenic; rather, it is N-nitroso compounds, such as nitrosamines, produced by the reaction between nitrites and meat protein that are. The curing process promotes the formation of nitrosamines due to the abundance of added nitrites, proteins and myoglobin whose heme group accelerates the reaction. Cooking at high temperatures (deep-frying) greatly accelerates the formation of nitrosamines. Government regulations limit the quantity of nitrites used to cure meats and requires the addition of neutralizing agents (antioxidants) in certain products, for example bacon. Nitrates naturally present in food mainly come from fruits and vegetables, which contain antioxidants, such as vitamin C and polyphenols that prevent the formation of N-nitroso compounds.

Up until about twenty years ago, nitrates and nitrites found in the human body were considered inert final products of the metabolism of nitric oxide (NO), a gas that acts as a signalling molecule and contributes to the regulation of blood flow and several other physiological functions. In the presence of oxygen, nitric oxide is produced in the endothelial cells that line blood vessels through the oxidizing reaction of the amino acid L-arginine into NO and L-citrulline. Several medications used to treat heart disease increase the signalling pathway of NO, either by increasing its bioavailability or by inhibiting its degradation. The most well-known are organic nitrates (e.g. nitroglycerine). They act by releasing NO rapidly and induce non-specific dilatation of both arteries and veins, which improves blood flow. Other pharmacological agents are phosphodiesterase-5 inhibitors, which are used to treat pulmonary hypertension and erectile dysfunction (e.g. sildenafil, better known by the brand name Viagra). Moreover, inhibitors of the HMG reductase enzyme (statins) and of the angiotensin-converting enzyme indirectly increase the bioavailability of NO.

Since 2001, we know that endogenous nitrites are an important alternative source of NO, particularly when oxygen levels are low, as is the case with blood microcirculation (see Figure 1). At that time, it was thought that the intake of nitrates and nitrites from food sources had no effect on blood vessels, since it was not thought that this intake could increase the circulating concentration of nitrites. We now know that dietary nitrates are quickly absorbed in the small intestine, about 75% of nitrates are excreted by the kidneys, and what is left becomes highly concentrated in the salivary glands (10 times the plasma concentration). When nitrates are secreted in saliva, they are converted to nitrites by the commensal bacteria, then swallowed with the saliva and absorbed into intestinal circulation. The circulating nitrites can be transformed into nitric oxide by different enzymes (reductases).

Figure 1. Formation and recycling of nitrates (NO3), nitrites (NO2) and nitric oxide (NO). Adapted from Woessner et al., 2017. In the presence of oxygen, endothelial nitric oxide synthase (eNOS) catalyzes the oxidation of L-arginine to NO. NO can also be quickly oxidized into nitrites and nitrates. A secondary source of vascular NO is obtained through diet. Consumption of foods high in inorganic nitrates (green leafy vegetables, beetroot) has been shown to increase plasma nitrate concentration,which can be secreted in saliva and reduced to nitrite by commensal bacteria in the mouth. Nitrites can then be further reduced to NO (and other biologically active nitrogen oxides) via several mechanisms that are expedited under hypoxic conditions. Hence, although some of the circulating nitrates and nitrites are excreted in the kidneys, they can also be recycled back to NO.

Dietary Sources of Nitrates
About 85% of dietary nitrates (NO3) come from vegetables, and the rest mostly from drinking water. Dietary nitrites (NO2) mostly come from cured meats (charcuterie). Vegetables can be grouped into 3 categories according to their nitrate content (see Table I). Vegetables high in nitrates (>1000 mg/kg) belong to the Brassicaceae (arugula), Chenopodiaceae (beetroot, spinach), Asteraceae (lettuce), and Apiaceae (celery) families. Most commonly eaten vegetables have medium levels of nitrates (100–1000 mg/kg), whereas onions and tomatoes contain very little nitrates (<100 mg/kg). Juicing vegetables is a popular and convenient way to increase vegetable consumption, and several commercial juices are available on the market. Whereas the nitrate content of homemade fresh juice is negligible, it increases dramatically after two days at room temperature, but remains low if stored in the refrigerator at 4 °C. The conversion of nitrates to nitrites in juices prepared at home is due to the presence of bacterial enzymes (reductases), which is less problematic in commercially prepared juices since they are lightly pasteurized.

Table I. Nitrate content in vegetables and water. Source: Lidder & Webb, 2012.

*Note: To facilitate the selection of vegetables to build a diet, the authors recommend using “nitrate units” (1 unit = 1 mmol) to ensure sufficient nitrate intake in order to benefit from the hypotensive effects or to improve exercise performance, and also to avoid consuming more nitrates than recommended (4.2 units for an adult weighing 70 kg).

The acceptable daily intake (ADI) established by the European Food Safety Authority for nitrates is 3.7 mg/kg (0.06 mmol/kg), which corresponds to about 260 mg (4.2 mmol) daily for an adult weighing 70 kg. This ADI was established by dividing the maximum harmless dose for rats and dogs by 100. According to estimations, Europeans consume 31–185 mg of nitrates daily and 0–20 mg of nitrites daily. Based on the moderate recommendation to eat 400 g of a variety of fruits and vegetables per day, the dietary intake of nitrates is about 157 mg/day. Several countries currently recommend a diet high in nitrates for people with heart disease. The DASH diet (Dietary Approach to Stop Hypertension), for example, with its emphasis on fruits and vegetables, whole grains, lean meats (poultry, fish) and nuts, provides a significant level of nitrates. In a clinical study, the DASH diet (rich in fruits and vegetables) lowered blood pressure in subjects with hypertension almost as much as a monotherapy with antihypertensive medication. In fact, it has been suggested that the cardioprotective effects of fruits and vegetables observed in epidemiological studies are caused by the high nitrate content of green leafy vegetables.

The choice of fruits and vegetables eaten can have an important impact on the quantity of dietary nitrates. For example, it is estimated that a DASH diet that only includes fruits and vegetables with low nitrate levels would provide 174 mg of nitrates and 0.41 mg of nitrites, whereas choosing fruits and vegetables high in nitrates can provide up to 1222 mg of nitrates and 0.35 of nitrites. This estimation indicates that the dietary intake of nitrates can vary up to about 700%, according to dietary choices. An excessive intake of nitrates, which is very rare, can cause methemoglobinemia, a disease or intoxication where the level of methemoglobin (a type of hemoglobin that cannot bind oxygen) is too high. Infants (<3 years) are much more susceptible than older children and adults to this disease. In children it is sometimes called “blue baby syndrome.” In adults, this intoxication is rare because their diet cannot contain nitrates in high enough quantities to cause the disease. However, infants can get sick by consuming 200 g of spinach high in nitrates/per day. The American Academy of Pediatrics recommends not giving children foods (purees) containing vegetables (e.g. spinach, beetroot, green beans, carrots) before the age of three months.

A prospective study published in 2018 revealed an association between urinary nitrate and the prevalence of heart disease and the risk of mortality. A concentration of nitrates in urine that was 10 times higher was associated with a 33% decreased risk of hypertension and a 39% decreased risk of stroke. However, there was no association between the concentration of nitrates in urine and the risk of myocardial infarction. Moreover, a ten-fold increase of urinary nitrates was associated with a reduction in all-cause mortality (–37%) and a reduction in cardiovascular mortality (–56%). Despite concerns that nitrates can be converted to nitrites and N-nitrosamines and become carcinogenic, nitrates in urine were not associated with cancer prevalence or cancer mortality. Future studies should evaluate whether nitrate supplements can prevent or reduce the prevalence of heart disease and premature death.

The Effect of Nitrates on Blood Pressure
study published in 2008 (randomized, placebo-controlled, crossover design) evaluated the effects of a diet high in nitrates on blood pressure in healthy, non-smoking and physically active participants. A diet high in nitrates led to a significant decrease in average blood pressure (3.2 mm Hg) and diastolic blood pressure (3.7 mm Hg), when compared to a diet low in nitrates. In this study, the daily dose of nitrate supplements taken corresponded to that normally contained in 150–250 g from vegetables high in nitrates, such as spinach, beetroot and lettuce. The authors note that the decrease in blood pressure observed in their study was similar to that observed in the DASH study in the healthy group that ate a diet rich in fruits and vegetables, when compared with the group that consumed few fruits and vegetables. In another study, drinking 500 ml of beetroot juice led to an even more significant decrease in systolic (~10.4 mm Hg) and diastolic (~8 mm Hg) blood pressure, when compared to the group that ingested the placebo (500 ml of water, crossover study). This effect was temporally correlated with the transient increase in plasma nitrite concentration. Interrupting the enterosalivary conversion cycle of nitrates to nitrites (by asking participants to spit out all their saliva for 3 hours after ingesting beetroot juice) completely prevented the increase of plasma nitrite concentration, and the decrease in blood pressure. This latter finding confirms that the decrease in blood pressure caused by the consumption of beetroot juice is due to the conversion of nitrates found in beetroot juice to nitrites.

Hypertension, Type 2 Diabetes, Hypercholesterolemia, Obesity
Even though the effect of nitrates on the decrease in blood pressure in healthy subjects was consistently reported in several studies, this is not always the case in studies among subjects with a chronic disease. In a British study of 68 subjects with hypertension, the blood pressure of those who drank 250 ml of beetroot juice daily for a month was lower by 8 mm Hg, compared to those who consumed beetroot juice depleted of nitrates (placebo). In a similar study, also among hypertensive subjects, no decrease in blood pressure was observed, even though the consumption of beetroot juice resulted in a considerable increase in plasma nitrite concentration. In another study of diabetics, there were no effects of dietary nitrites (beetroot juice) on blood pressure, endothelial function, and insulin sensitivity. However, supplementing the diet with beetroot juice significantly reduced systolic blood pressure of overweight or obese participants, aged 55 to 70, when compared to supplementation with blackcurrant juice, which was very low in nitrates. Finally, a study among 69 participants with hypercholesterolemia showed that the intake of dietary nitrates improved vascular function when compared to the group that received the placebo. The reason for variability of the results obtained in these clinical studies is unknown. Length of the treatment, medications used to manage hypertension, methods used to measure blood pressure, and differences between cohorts (e.g. age, BMI, diminished response to NO in certain diseases) are among possible explanatory factors.

Heart Failure
recent study (randomized, placebo-controlled, crossover design) shows that dietary nitrate supplementation (beetroot juice) increases exercise performance in people with heart failure with reduced ejection fraction. Here is a summary of the study and the main results. After consuming 140 ml of concentrated beetroot juice, the plasma nitrate and nitrite concentration of subjects increased on average by 15 times (1469%) and 2 times (105%), respectively, and the concentration of nitric oxide (a gas) in breath increased by 60%. This effect was not observed with the placebo, a beetroot juice previously depleted of nitrates and that could not be differentiated from the original beetroot juice (packaging, colour, texture, taste and smell) by the study subjects. Two hours after consuming the beetroot juice, subjects exercised for a few minutes on an ergometer stationary bike in a semi-reclined position at various intensities. Respiratory gas exchange was measured continuously. Heart rate, blood pressure and perceived fatigue were evaluated during the last 30 seconds of each phase. Consumption of nitrates had no effect on the ventilatory response, or exercise efficiency, heart rate, and blood pressure. However, compared to the placebo group, the subjects that ingested the beetroot juice were able to reach peak oxygen consumption (VO2 peak) that was higher by 8%, and increased, on average, their duration of effort to exhaustion by 7%. These findings suggest that dietary nitrate intake could be a valuable addition to the management of exercise intolerance among patients with heart failure with reduced ejection fraction.

Nitrates and Athletic Performance
Several studies have been conducted on the impact of nitrate supplementation on the performance of amateur and competitive athletes. In one study, 10 young men drank concentrated beetroot juice or a placebo and, after 2.5 hours (to coincide with the maximum concentration of circulating nitrites), did moderate to high intensity physical activity. When compared to the placebo group, consuming 70 ml of beetroot juice had no effect on athletic performance, but ingesting 140 ml or 280 ml of juice reduced oxygen consumption during moderate physical activity by 1.7% and 3.0%, whereas average time–to-task failure(at very high intensity) increased from 8 min 18 s to 9 min 30 s (14%) and from 8 min 13 s to 9 min 12 s (12%), respectively. Such an increase (12–14%) can seem enormous, but in fact translates to about a 1 to 2% reduction in time to complete a race, for example. In an elite sport, a 1% difference is considered very significant, reducing the time it takes to race a 1,500-metre distance by about 2 seconds and that of a 3,000-metre distance by about 4–5 seconds, for example. Other studies have shown a reduction in oxygen consumption (for the same effort) and an improvement in performance for walking, running, rowing, and cycling, through nitrate supplementation (beetroot juice or NaNO3). A meta-analysis of 17 of these studies shows that nitrates give a small advantage in performance for time to exhaustion tests, and have a slight beneficial, but not statistically significant, effect on performance during time trials. Another meta-analysis, published in 2016, including 26 randomized, placebo-controlled studies, indicates that nitrate supplementation significantly reduces oxygen consumption for a given effort during a moderate to high intensity exercise in healthy individuals, but not in people with a chronic disease.

Beetroot juice and other supplements with high nitrate levels are obviously not a cure-all. It is better to adopt a global approach to stay healthy, i.e. exercise daily and follow a healthy diet (Mediterranean for example) and eat several servings of fruits and vegetables every day, including green vegetables rich in nitrates, fibre, minerals and vitamins.

The effects of coffee on cardiovascular disease

The effects of coffee on cardiovascular disease

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.