The cardiovascular benefits of avocado

The cardiovascular benefits of avocado

OVERVIEW

  • Avocado is an exceptional source of monounsaturated fat, with content similar to that of olive oil.
  • These monounsaturated fats improve the lipid profile, in particular by raising HDL-cholesterol levels, a phenomenon associated with a reduced risk of cardiovascular disease.
  • A recent study confirms this cardioprotective potential of avocado, with a 20% reduction in the risk of coronary heart disease observed in regular consumers (2 or more servings per week).

There is currently a consensus in the scientific community on the importance of favouring dietary sources of unsaturated fats (especially monounsaturated and omega-3 polyunsaturated fats) to significantly reduce the risk of cardiovascular disease and premature mortality (see our article on this subject). With the exception of fatty fish rich in omega-3 (salmon, sardines, mackerel), plant-based foods are the main sources of these unsaturated fats, particularly oils (olive oil and those rich in omega-3 like canola oil), nuts, certain seeds (flax, chia, hemp) as well as fruits such as avocado. Regular consumption of these foods high in unsaturated fats has repeatedly been associated with a marked decrease in the risk of cardiovascular events, a cardioprotective effect that is particularly well documented for extra-virgin olive oil and nuts.

A unique nutritional profile
Although the impact of avocado consumption has been less studied than that of other plant sources of unsaturated fat, it has been suspected for several years that this fruit also exerts positive effects on cardiovascular health. On the one hand, avocado stands out from other fruits for its exceptionally high monounsaturated fat content, with a content (per serving) similar to that of olive oil (Table 1). On the other hand, a serving of avocado contains very high amounts of fibre (4 g), potassium (350 mg), folate (60 µg), and several other vitamins and minerals known to participate in the prevention of cardiovascular disease.

Table 1. Comparison of the lipid profile of avocado and olive oil. The data corresponds to the amount of fatty acids contained in half of a Haas avocado, the main variety consumed in the world, or olive oil (1 tablespoon or 15 mL). Taken from USDA. FoodData Central.

Fatty acidsAvocado (68 g)Olive oil (15 mL)
Total10 g12.7 g
Monounsaturated6.7 g9.4 g
Polyunsaturated1.2 g1.2 g
Saturated1.4 g2.1 g

This positive impact on the heart is also suggested by the results of intervention studies that examined the impact of avocado on certain markers of good cardiovascular health. For example, a meta-analysis of 7 studies (202 participants) indicates that the consumption of avocado is associated with an increase in HDL cholesterol and a decrease in the ratio of total cholesterol to HDL cholesterol, a parameter which is considered to be a good predictor of coronary heart disease mortality. A decrease in triglycerides, total cholesterol and LDL cholesterol levels associated with the consumption of avocado has also been reported, but is, however, not observed in all studies. Nevertheless, the increase in HDL cholesterol observed in all the studies is very encouraging and strongly suggests that avocado could contribute to the prevention of cardiovascular disease.

A cardioprotective fruit
This cardioprotective potential of avocado has just been confirmed by the results of a large-scale epidemiological studycarried out among people enrolled in two large cohorts headed by Harvard University, namely the Nurses’ Health Study (68,786 women) and the Health Professionals Follow-up Study (41,701 men). Over a period of 30 years, researchers periodically collected information on the dietary habits of participants in both studies and subsequently examined the association between avocado consumption and the risk of cardiovascular disease.

The results obtained are very interesting: compared to people who never or very rarely eat them, regular avocado consumers have a risk of coronary heart disease reduced by 16% (1 serving per week) and 21% (2 servings or more per week) (Figure 1).

Figure 1. Association between the frequency of avocado consumption and the risk of coronary heart disease. The quantities indicated refer to one serving of avocado, corresponding to approximately half of the fruit. Taken from Pacheco et al. (2022).

There are therefore only benefits to integrating avocado into our eating habits, especially if its monounsaturated fats replace other sources of fats that are less beneficial to health. According to the researchers’ calculations, replacing half a serving of foods rich in saturated fat (butter, cheese, deli meats) with an equivalent quantity of avocado would reduce the risk of cardiovascular disease by approximately 20%.

Avocados are increasingly popular, especially among young people, and are even predicted to become the 2nd most traded tropical fruit by 2030 globally, just behind bananas. In light of the positive effects of these fruits on cardiovascular health, we can only welcome this new trend.

Obviously, the high demand for avocado creates strong pressures on the fruit’s production systems, particularly in terms of deforestation for the establishment of new crops and increased demand for water. However, it is important to note that the water footprint (the amount of water required for production) of avocado is much lower than that of all animal products, especially beef (Table 2). In addition, as is the case for all plants, the carbon footprint of avocado is also much lower than that of animal products, the production of an avocado generating approximately 0.2 kg of CO2-eq compared to 4 kg for beef.

Table 2. Comparison of the water footprint of avocado and different foods of animal origin. Taken from UNESCO-IHE Institute for Water Education (2010) 

FoodWater footprint
(m3/ton)
Beef15,400
Lamb and sheep10,400
Porc6,000
Chicken4,300
Eggs3,300
Avocado1,981

The influence of oral health on the risk of cardiovascular disease

The influence of oral health on the risk of cardiovascular disease

OVERVIEW

  • Periodontitis is an inflammatory reaction affecting the periodontium, i.e., all the structures responsible for anchoring the teeth (gums, ligaments, alveolar bone).
  • A very large number of studies have observed a close link between periodontitis and an increased risk of several pathologies, including myocardial infarction and stroke.
  • The expansion of health insurance to cover dental care would therefore be an important step forward for cardiovascular prevention and the prevention of several other chronic diseases.

It is now clearly established that the microbiome, the vast bacterial community that lives in symbiosis with us, plays an essential role in the functioning of the human body and the maintenance of good health. This link is particularly well documented with regard to the intestinal microbiome, that is, the hundreds of billions of bacteria that are located in the digestive system, in particular at the level of the colon. In recent years, an impressive number of studies have shown that these bacteria play a leading role in the proper functioning of the metabolism and the immune system and that imbalances in the composition of the microbiome are associated with the development of several chronic diseases.

Oral microbiome
The mouth represents another privileged site of colonization by bacteria; each mL of saliva from a healthy adult contains approximately 100 million bacterial cells, not to mention the millions of bacteria present in other areas of the oral cavity, such as dental plaque, tongue, cheeks, palate, throat and tonsils. It is therefore not surprising that a simple 10-second kiss with tongue contact and exchange of saliva (French kiss) can transfer around 80 million bacteria between partners!

On average, the human mouth contains about 250 distinct bacterial species, from the approximately 700 species of oral bacteria that have been identified so far. The composition of this bacterial community is unique to each person and is influenced by their genetics, age, place of residence, cohabitation with other people, the nature of the diet and, obviously, the frequency of oral hygiene care.

In a healthy mouth, the oral bacterial community is a balanced ecosystem that performs several beneficial functions for the host. For example, some bacteria have anti-inflammatory activity that can block the action of certain pathogens, while others reduce the acidity of dental plaque (through the production of basic compounds such as ammonia) and thus prevent the demineralization of teeth, the first step in the process of tooth decay. Oral bacteria also have the ability to convert nitrates found in fruits and vegetables into nitric oxide (NO), a vasodilator that helps control blood pressure (see our article on this subject).

Disturbed ecosystem
It is the disruption of this balance of the bacterial ecosystem (dysbiosis) that is the trigger for the two main diseases affecting the teeth, namely dental caries and periodontal disease. In the case of caries, the cause is the establishment of a bacterial community enriched in certain species (Streptococci of the mutans group, in particular), capable of fermenting dietary sugars and reducing the pH sufficiently to initiate the demineralization of the tooth. The action of these bacteria is however local, restricted to the level of tooth enamel, and therefore generally does not have a major impact on health in general.

The global repercussions associated with periodontal diseases are much more serious, and it is for this reason that these infections have attracted a great deal of interest from the scientific and medical communities in recent years. Not only with regard to the identification of the bacteria responsible for these infections and their mechanisms of action, but also, and perhaps above all, because of the close relationship observed in several epidemiological studies between periodontitis and several serious chronic diseases, including cardiovascular disease, diabetes, certain cancers and even Alzheimer’s disease.

Periodontitis
As its name suggests, periodontitis is an inflammatory reaction affecting the periodontium, i.e., all the structures responsible for anchoring the teeth (gums, ligaments, alveolar bone) (Figure 1). Periodontitis begins in the form of gingivitis, which is local inflammation of the gums caused by bacteria present in dental plaque (the bacterial biofilm that forms on the teeth). This inflammation is usually quite benign and reversible, but can progress to chronic periodontitis in some more susceptible individuals. There is then a gradual resorption of the gums, ligaments and alveolar bone, which causes the appearance of periodontal pockets around the tooth and, eventually, its fall. Periodontal disease is one of the most common chronic inflammatory diseases, affecting almost 50% of the population to varying degrees, including 10% who develop severe forms of the disease, and is one of the main causes of tooth loss.

Figure 1. Schematic illustration of the main features of periodontitis. Image from Shutterstock.

The trigger factor for periodontitis is an imbalance in the composition of the microbial community present in dental plaque that promotes the growth of pathogenic species responsible for this infection. Among the approximately 400 different species of bacteria associated with dental plaque, the presence of a complex composed of the anaerobic bacteria Porphyromonas gingivalis, Treponema denticola, and Tanneralla forsythia (known as the red complex) is closely correlated with clinical measures of periodontitis, and more particularly with advanced periodontal lesions, and could therefore play an important role in the development of these pathologies. It is also interesting to note that the analysis of human skeletons has revealed that periodontitis became more frequent around 10,000 years ago (in the Neolithic period) and that this increase coincides with the increased presence of one of these bacteria (P. gingivalis) in dental plaque. It is likely that this change in plaque microbial composition is a consequence of changes in the human diet introduced by agriculture, in particular a higher carbohydrate intake.

A disproportionate inflammatory response
It is the exaggerated inflammatory response caused by the presence of this bacterial imbalance in dental plaque that is largely responsible for the development of periodontitis (Figure 2).


Figure 2. Impact of inflammation generated by bacterial imbalance (dysbiosis) on the development of periodontitis.
In a healthy mouth (left figure), the bacterial biofilm is in balance with the host’s immune system and does not generate an inflammatory response. Disruption of this balance (by poor dental hygiene or smoking, for example) can cause gingivitis, which is a mild inflammation of the gums characterized by the formation of a slight gingival crevice (≤ 3 mm deep), but without bone damage. Gingivitis can progress to periodontitis when the bacterial imbalance of the biofilm induces a strong inflammatory reaction that destroys the tissues surrounding the tooth to form deeper periodontal pockets (≥ 4 mm) and the destruction of the alveolar bone. From Hajishengallis (2015).

When they manage to colonize the subgingival space, pathogenic bacteria such as P. gingivalis secrete numerous virulence factors (proteases, hemolytic factors, etc.) that degrade the tissues present at the site of infection and generate the essential elements for the growth of these bacteria. The bleeding gums caused by this infection is particularly beneficial for P. gingivalis since the growth of this bacterium requires a high supply of iron, present in the heme group of the hemoglobin of red blood cells.

The immune system obviously reacts strongly to this microbial invasion (which can reach several hundred million bacteria in certain deep periodontal pockets) by recruiting at the site of infection the first-line innate immunity (neutrophils, macrophages), specialized in the rapid response to the presence of pathogens. There is then massive production of cytokines, prostaglandins, and matrix metalloproteinases by these immune cells which, collectively, create a high-intensity inflammation intended to eliminate the bacteria present in the periodontal tissues.

However, this inflammatory response does not have the expected effects at all. On the one hand, periodontal bacteria have developed several subterfuges to escape the immune response and are therefore little affected by the host response; on the other hand, the continuous presence of an inflammatory microenvironment causes considerable damage to the periodontal tissues, which accelerates their destruction and the resorption of the gums, ligaments and bone characteristic of periodontitis. This inflammatory attack on the periodontium also has the perverse effect of generating several essential nutrients for bacterial growth, which further amplifies the infection and accelerates the degradation of the tissues surrounding the tooth. In other words, periodontitis is the result of a vicious circle in which the bacterial imbalance associated with dental plaque provokes a strong inflammatory immune response, with this inflammation leading to the destruction of the periodontal tissues, which in turn promotes the growth of these bacteria (Figure 3).

Figure 3. Amplification of the inflammatory response is responsible for the development of periodontitis. The imbalance of the microbiome of dental plaque (dysbiosis) leads to the activation of the immune defences (mainly the complement system and the Toll-like receptors (TLR)) and the triggering of an inflammatory response. This inflammation causes the destruction of the tissues surrounding the tooth, including the alveolar bone, which generates several nutrients that support the proliferation of pathogenic bacteria, adapted to grow in these inflammatory conditions. An amplification loop is therefore created in which inflammation promotes bacterial growth and vice versa, which supports the progression of periodontitis.

The mechanisms involved in this “immunodestruction” are extraordinarily complex and will not be described in detail here, but let us only mention that the sustained presence of periodontal bacteria activates certain defence systems specialized in the rapid response to infections (Toll-like receptors and complement system) present on the surface of immune cells, which activates the production of inflammatory molecules that are very irritating to the surrounding tissues. In the alveolar bone, for example, the production of cytokines (interleukin-17, in particular) stimulates the cells involved in the breakdown of bone tissue (osteoclasts) and leads to bone resorption.

It is important to mention that even if the initiation of periodontitis depends on the presence of pathogenic bacteria in dental plaque, the evolution of the disease remains strongly influenced by several factors, both genetic and associated with lifestyle. For example, there is a strong genetic predisposition to periodontal disease, with an estimated heritability of 50%: some people do not develop periodontitis despite a massive build-up of tartar (and bacteria) around the teeth, while others will be affected by the disease despite a small amount of dental plaque. These differences in susceptibility to periodontitis are thought to be caused by the presence of variations (polymorphisms) in certain genes involved in the inflammatory response.

In terms of lifestyle habits, the nature of the diet, certain metabolic diseases such as obesity and type 2 diabetes, stress and smoking are well-documented aggravating factors for periodontitis. This influence is particularly dramatic for smoking, which has catastrophic effects on the onset, progression and severity of periodontitis, with an increase in the risk of the disease that can reach more than 25 times (see Table 3). It should be noted that a common point to all of these risk factors is that they all influence in one way or another the degree of inflammation, which highlights to what extent the development of periodontitis depends on the intensity of the host’s inflammatory response in reaction to the presence of pathogenic bacteria in dental plaque.

Periodontitis and cardiovascular disease
Although the damage caused by this disproportionate inflammatory response is first and foremost local, at the level of the tissues surrounding the tooth, the fact remains that the inflammatory molecules that are generated at the site of infection are in close contact with the bloodstream and can therefore diffuse into the blood and affect the whole body. The impact of this systemic inflammation is probably very important, as numerous studies have reported that the incidence of periodontitis is strongly correlated with the presence of several other diseases (comorbidities) whose development is influenced by chronic inflammation, in particular cardiovascular disease, diabetes, certain cancers and arthritis (Table 1).

Table 1. Association of periodontitis with different pathologies.

Comorbidities of periodontitisObserved phenomenaSources
Cardiovascular diseasePeriodontitis is associated with an increased risk of heart attack and stroke.See Table 2 references.
Diabetes (types 1 and 2)Chronic inflammation associated with diabetes accelerates the destruction of periodontal tissues.Lalla and Papapanou (2011)
This association between the two diseases is bidirectional, as the chronic inflammation generated by periodontitis increases insulin resistance and in turn disrupts blood sugar control.
Alzheimer'sSeveral epidemiological studies have reported an association between periodontitis and the risk of developing Alzheimer’s disease.Dioguardi et al. (2020)
The periodontal bacterium P. gingivalis (DNA, proteases) has been detected in the brains of patients who have died of Alzheimer’s disease as well as in the cerebrospinal fluid of people suffering from the disease. Dominy et al. (2019)
The risk of mortality from Alzheimer’s disease is correlated with antibody levels to a group of periodontal bacteria, including P. gingivalis, Campylobacter rectus, and Prevotella melaninogenica.Beydoun et al. (2020)
Rheumatoid arthritisSeveral epidemiological studies have observed an association between periodontitis and rheumatoid arthritis.Sher et al. (2014)
The inflammation caused by periodontitis stimulates the production of cells that increase bone resorption in the joints.Zhao et al. (2020)
CancerThe incidence of colorectal cancer is 50% higher in individuals with a history of periodontitis.Janati et al. (2022)
A periodontal bacterium (Fusobacterium nucleatum) has been repeatedly observed in colorectal cancers. Castellarin et al. (2011)
High levels of P. gingivalis have been detected in oral cancers.Katz et al. (2011)
High levels of antibodies against P. gingivalis are associated with a 2-fold higher risk of pancreatic cancer. Michaud et al. (2013)
Liver diseasesPeriodontitis is correlated with an increased incidence of liver disease.Helenius-Hietala et al. (2019)
In patients with fatty liver disease or non-alcoholic steatohepatitis, treatment of periodontitis decreases blood levels of markers of liver damage.Yoneda et al. (2012)
Intestinal diseasesChronic inflammatory bowel disease is associated with an increased risk of periodontitis.Papageorgiou et al. (2017)
This relationship is bidirectional, as periodontal bacteria ingested via saliva contribute to intestinal inflammation and disrupt the microbiome and intestinal barrier.Kitamoto et al. (2020)
Pregnancy complicationsMaternal periodontitis is associated with a higher risk of undesirable pregnancy outcomes such as miscarriages, premature deliveries, and low birth weight.Madianos et al. (2013)
Periodontal bacteria (P. gingivalis, F. nucleatum) have been observed in the placenta and clinical studies have reported a link between the presence of these bacteria and pregnancy complications.Han and Wang (2013)

The link between periodontitis and cardiovascular disease has been particularly studied because it is clearly established that inflammation participates in all stages of the development of atherosclerosis, from the appearance of the first lesions caused by the infiltration of white blood cells which store cholesterol, until the formation of clots that block blood circulation and cause heart attack and stroke. These inflammatory conditions are usually a consequence of certain lifestyle factors (smoking, poor diet, stress, physical inactivity), but can also be created by acute infections (influenza and COVID-19, for example) or chronic infections (Chlamydia pneumoniae, Helicobacter pylori, human immunodeficiency virus). Since all of these infections increase the risk of cardiovascular disease, it is therefore possible that a similar phenomenon exists for the chronic inflammation that results from periodontitis.

The first clue to the existence of a link between periodontitis and the risk of cardiovascular disease comes from a study published in 1989, where it was observed that a group of patients who had suffered a myocardial infarction had poorer oral health (more cavities, gingivitis, periodontitis) than a control group. Since then, hundreds of studies examining the issue have confirmed this association and shown that the presence of oral health problems, periodontitis in particular, is very often correlated with an increased risk of heart attack and stroke (Table 2).

 

Table 2. Summary of the main studies reporting an association between periodontitis and the risk of heart attack and stroke.

Measured parameterObserved phenomenonSources
Coronary artery diseasePeriodontitis is associated with an increased risk of heart attack (men < 50 years).DeStefano et al. (1993)

Poor oral health (caries, periodontitis) is associated with an increased risk of heart attack and sudden death in coronary patients.Mattila et al. (1995)
Tooth loss caused by periodontitis is associated with an increased risk of heart attack and sudden death.Joshipura et al. (1996)
Bone loss caused by periodontitis is associated with an increased risk of heart attack, fatal and non-fatal.Beck et al. (1996)
The severity of periodontitis (bone loss) is associated with an increased risk of heart attack.Arbes et al. (1999)
Periodontitis is associated with an increased risk of fatal infarction.Morrison et al. (1999)
Periodontitis is associated with a slight (non-significant) increase in the risk of coronary heart attacks.Hujoel et al. (2000)
Periodontitis is associated with a slight (non-significant) increase in the risk of heart attack.Howell et al. (2001)
Bleeding gums are correlated with a higher risk of heart attack.Buhlin et al. (2002)
Periodontitis is associated with a higher risk of hospitalization for heart attack, angina or unstable angina.López et al. (2002)
High levels of antibodies against two pathogens responsible for periodontitis (A. actinomycetemcomitans and P. gingivalis) are associated with an increased risk of coronary heart disease.Pussinen et al. (2003)
Coronary patients more often experience poor oral health and an increase in inflammatory markers.Meurman et al. (2003)
Periodontitis is associated with an increased risk of mortality from coronary heart disease.Ajwani et al. (2003)
High levels of antibodies against a bacterium responsible for periodontitis (P. gingivalis) are associated with an increased risk of heart attack.Pussinen et al. (2004)
Periodontitis is associated with an increase (15%) in the risk of coronary heart disease (meta-analysis).Khader et al. (2004)
Periodontitis, combined with tooth loss, is associated with an increased risk of coronary heart disease.Elter et al. (2004)
Oral pathologies are more common in coronary patients.Janket et al. (2004)
Periodontitis is more common in coronary patients.Geerts et al. (2004)
High levels of antibodies against the bacteria responsible for periodontitis are associated with an increased risk of coronary heart disease in both smokers and non-smokers.Beck et al. (2005)
Higher levels of antibodies to bacteria involved in periodontitis (P. gingivalis and A. actinomycetemcomitans) are associated with an increased risk of coronary heart disease.Pussinen et al. (2005)
The presence of deep periodontal pockets is more common in women with coronary artery disease.Buhlin et al. (2005)
Periodontitis is associated with a higher risk of acute infarction.Cueto et al. (2005)
Periodontitis and levels of pathogenic bacteria (A. actinomycetemcomitans in particular) in the subgingival biofilm are associated with an increased risk of coronary heart disease.Spahr et al. (2006)
Periodontitis is more common in patients with coronary artery disease.Geismar et al. (2006)
Poor periodontal health is associated with an increased risk of coronary heart disease.Briggs et al. (2006)
Gingivitis, cavities and tooth loss are all associated with an increased risk of angina.Ylostalo et al. (2006)
Patients with acute coronary syndrome are at greater risk of being affected by periodontitis simultaneously.Accarini and de Godoy (2006)
The severity of periodontitis (bone loss) is associated with an increased risk of heart attack in 40-60 year-olds.Holmlund et al. (2006)
Patients affected by periodontitis have an increased risk (15%) of coronary heart disease (meta-analysis).Bahekar et al. (2007)
Periodontitis is associated with an increased risk of acute coronary syndrome.Rech et al. (2007)
Patients with acute coronary syndrome are more likely to have oral microbial flora enriched with periodontitis-causing bacteria.Rubenfire et al. (2007)
Periodontitis is associated with an increased risk of heart attack in both men and women.Andriankaja et al. (2007)
Coronary patients have deeper periodontal pockets and higher levels of a bacterium (Prevotella intermidia) involved in periodontitis.Nonnenmacher et al. (2007)
Men and women with < 10 teeth have a higher risk of coronary heart disease than those with > 25 teeth.Hung et al. (2007)
The severity of coronary artery disease (number of vessels affected) is correlated with the severity of periodontal disease.Gotsman et al. (2007)
Severe periodontitis is more common in patients with coronary artery disease.Starkhammar Johansson et al. (2008)
Chronic periodontitis is associated with an increased risk of coronary heart disease in men < 60 years of age.Dietrich et al. (2008)
Periodontitis is associated with an increased risk of angina and heart attack in both men and women.Senba et al. (2008)
Higher levels of antibodies to bacteria involved in periodontitis (P. gingivalis, A. actinomycetemcomitans, T. forsythia, and T. denticola) are associated with an increased risk of heart attack.Lund Håheim et al. (2008)
Higher levels of antibodies to bacteria involved in periodontitis (P. gingivalis and A. actinomycetemcomitans) are associated with increased coronary artery calcification in type 1 diabetics.Colhoun et al. (2008)
The severity of periodontitis is correlated with greater blockage of the coronary arteries.Amabile et al. (2008)
The risk of coronary injury is higher (34%) in patients with periodontitis (meta-analysis).Blaizot et al. (2009)
Periodontitis is associated with a 24-35% increase in the risk of coronary heart disease (meta-analysis).Sanz et al. (2010)
Mortality from coronary heart disease is 7 times higher in patients with < 10 teeth compared to those with > 25 teeth.Holmlund et al. (2010)
High levels of two bacteria involved in periodontitis (Tannerella forsythensis and Prevotella intermedia) are correlated with an increased risk of heart attack.Andriankaja et al. (2011)
Periodontitis is associated with a higher risk of heart attack, regardless of smoking and diabetes.Rydén et al. (2016)
Periodontitis is associated with a twice as high risk of a heart attack (meta-analysis).Shi et al. (2016)
Patients with periodontitis are at higher risk of heart attack, cardiovascular mortality and all-cause mortality.Hansen et al. (2016)
Periodontitis doubles the risk of a heart attack (meta-analysis).Xu et al. (2017)
Oral infections in childhood (including cavities and periodontitis) are associated with the thickening of the carotid wall in adulthood.Pussinen et al. (2019)
Periodontitis and tooth loss are associated with a higher risk of coronary heart disease (meta-analysis).Gao et al. (2021)
Inflammation caused by periodontitis is associated with an increased risk of cardiovascular events.Van Dyke et al. (2021)
People affected by periodontitis have an increased risk of coronary heart attacks and premature mortality.Bengtsson et al. (2021)
StrokeBone loss caused by periodontitis is associated with an increased risk of stroke.Beck et al. (1996)
Poor oral health is associated with an increased risk of stroke in men > 60 years of age.Loesche et al. (1998)
Severe gingivitis, periodontitis and tooth loss are associated with an increased risk of fatal stroke.Morrison et al. (1999)
Periodontitis is associated with an increased risk of stroke (non-hemorrhagic).Wu et al. (2000)
Periodontitis is associated with a slight (non-significant) increase in the risk of stroke.Howell et al. (2001)
Bleeding gums are associated with a higher risk of stroke.Buhlin et al. (2002)
Periodontitis and tooth loss (< 24 teeth) are associated with an increased risk of stroke.Joshipura et al. (2003)
The risk of stroke associated with periodontitis is 2 times higher than the risk of coronary heart disease (2.85 vs 1.44)Janket et al. (2003)
Severe periodontitis (bone loss) is associated with an increased risk of stroke.Elter et al. (2003)
Severe periodontitis is associated with an increased risk of stroke.Dorfer et al. (2004)
High levels of antibodies against two pathogens responsible for periodontitis (A. actinomycetemcomitans and P. gingivalis) are associated with an increased risk of stroke (primary and secondary).Pussinen et al. (2004)
Periodontitis is associated with an increased risk of stroke in men < 60 years of age.Grau et al. (2004)
Higher-than-normal tooth loss is associated with a higher risk of stroke-related mortality and all-cause mortality.Abnet et al. (2005)
Poor periodontal health is associated with an increased risk of stroke.Lee et al. (2006)
Higher levels of antibodies to a bacterium involved in periodontitis (P. gingivalis) are associated with an increased risk of stroke.Pussinen et al. (2007)
Loss of > 9 teeth is associated with an increased risk of stroke.Tu et al. (2007)
Periodontitis is associated with an increased risk of stroke in 60-year-old and normotensive men.Sim et al. (2008)
The loss of > 7 teeth is associated with an increased risk of stroke (ischemic and hemorrhagic).Choe et al. (2009)
Bone loss caused by periodontitis is associated with a higher risk of stroke, especially in men < 65 years of age.Jimenez et al. (2009)
The loss of > 17 teeth is associated with an increase in inflammatory markers and an increased risk of stroke.You et al. (2009)
Periodontitis is associated with an increased risk of fatal stroke.Holmlund et al. (2010)
Periodontitis (periodontal pocket > 4.5 mm) is associated with an increased risk of stroke.Pradeep et al. (2010)
Periodontitis is associated with an increased risk of hemorrhagic stroke in obese men.Kim et al. (2010)
Patients with periodontitis are at greater risk of stroke, cardiovascular mortality and all-cause mortality.Hansen et al. (2016)
Periodontitis is associated with an increased risk of carotid atherosclerosis (meta-analysis)Zeng et al. (2016)
The severity of periodontitis is associated with an increased risk of stroke. Conversely, regular dental care is associated with a decreased risk.Sen et al. (2018)
Periodontitis is associated with an increased risk of stroke affecting the major arteries.Mascari et al. (2021)

 

Bacterial invasion
In addition to the chronic inflammation generated by gum infection, it has also been proposed that damage to periodontal tissues may provide bacteria with an entry point into the circulation, a phenomenon similar to that frequently observed for many pathogen agents (about 50 bacterial species and many viruses). One of the best examples is arguably endocarditis, an infection that occurs when bacteria from dental plaque enter the bloodstream through the gums and attach themselves to the inner walls of the heart chambers and valves. It is for this reason that patients who need to undergo surgery to treat valvular heart conditions (the replacement or repair of heart valves) and who have dental problems are referred to their dentist to treat these conditions before the operation to prevent postoperative valve infection. In addition, patients with prosthetic heart valves or valvular pathologies are prescribed antibiotics before dental procedures to prevent endocarditis (bacterial infection of a heart valve).

Bacteremia (presence of bacteria in the blood) associated with periodontitis also allows pathogens to come into contact with the wall of blood vessels and penetrate the endothelial and muscle cells of these vessels, including at the level of atherosclerotic plaques. In this sense, it should be noted that infection with the main periodontal bacterium (P. gingivalis) is associated with an acceleration of the development of atherosclerosis in animal models, possibly in response to the innate inflammatory immune response directed against the bacterium at the vessel level. In sum, the link between periodontitis and cardiovascular disease is biologically plausible, whether due to the diffusion of inflammatory molecules that diffuse into the circulation or the presence of bacteria in the vessels.

Common risk factors
As a statement from the American Heart Association on the matter points out, however, it is difficult to demonstrate that these associations are causal, i.e., that periodontitis is directly responsible for the increased risk of CVD observed in these studies. This difficulty is largely due to the fact that the risk factors for periodontitis are very similar to those responsible for CV diseases (which are called in epidemiology confounding factors, i.e., variables that may influence both the risk factor and the disease being studied) (Table 3). The best example is undoubtedly smoking, which is both the most important risk factor for cardiovascular disease and periodontitis, but this similarity is also observed for all the “classic” cardiovascular risk factors, whether hypertension, diabetes, obesity, hypercholesterolemia or poor diet. In other words, what increases the risk of periodontitis also increases the risk of cardiovascular disease and vice versa, which makes it very difficult to establish a causal link between the two diseases.

Table 3. Similarity between risk factors for cardiovascular disease and periodontitis.

Cardiovascular risk factorsImpact on the risk of periodontitisSources
SmokingCompared to non-smokers, the risk of periodontitis is 18 times higher in smokers aged 20–49 and 25 times higher in smokers aged 50 and over.Hyman and Reid (2003)
HypertensionPeriodontitis, especially severe forms of the disease, is associated with higher systolic and diastolic pressures and an increased risk of hypertension (≥140 mmHg systolic, ≥90 mmHg diastolic).Aguilera et al. (2020)
DyslipidemiasPeriodontitis is associated with higher levels of LDL cholesterol and triglycerides, as well as lower levels of HDL cholesterol.Nepomuceno et al. (2017)
Diabetes (types 1 and 2)See Table 1
ObesityObesity, especially at the abdominal level, is associated with a higher prevalence of periodontitis in young adults. Al-Zahrani et al. (2003)
Diet quality
Fruit and vegetable deficiencyA diet rich in fruits and vegetables is associated with a decreased risk of periodontitis.Dodington et al. (2015)
Fibre and whole-grain deficiencyHigh fibre intake is associated with lower prevalence and severity of periodontitis. Nielsen et al. (2016)
The protective effect of fibre contributes to the decrease in the risk of periodontitis associated with a high intake of whole grains.Merchant et al. (2006)
High intake of simple carbohydrates Consumption of added sugars is associated with an increase of about 50% in the prevalence of periodontitis (and caries).Lula et al. (2014)
High intake of saturated fatsA greater portion of energy intake in the form of saturated fats is associated with an increased risk of periodontitis, possibly due to the pro-inflammatory action of these fatty acids.Iwasaki et al. (2011)

That being said, some studies have tried to establish this link by adjusting the risk of periodontitis to take into account the impact of these confounding factors. For example, the Swedish PAROKRANK study reported a significant increase (28%) in the risk of a first heart attack in people affected by periodontitis, even after subtracting the contribution of the main cardiovascular risk factors. According to the currently available clinical data, it is estimated that periodontitis could be an independent risk factor for cardiovascular disease, with an increase of about 10–15% in risk.

Beneficial treatment
A causal link between periodontitis and cardiovascular disease is also suggested by certain studies showing that periodontal treatments (scaling and root planing) are associated with an improvement in certain cardiovascular health parameters and/or a decrease in cardiovascular events. For example, in patients with periodontitis, removal of subgingival plaque by root planing (under local anesthesia) resulted in improved endothelial function (dilation of vessels by blood flow) within 6 months of treatment. Several other studies have confirmed this positive impact of periodontal treatment on vessel function as well as on other important parameters of cardiovascular health, such as levels of inflammatory molecules and cholesterol levels (total, LDL and HDL). This improvement is particularly noticeable in patients with comorbidities such as metabolic syndrome, diabetes or cardiovascular disease, suggesting that periodontal treatment may be useful for patients at high risk of cardiovascular events. In this sense, it is interesting to note that a recent study reported that periodontal treatment of patients with a recent stroke was associated with a decrease in the overall risk of cardiovascular events in the following year, as measured by a combination of the incidence of stroke, infarction and sudden death.

Overall, these studies raise the possibility that the development of cardiovascular disease may indeed be directly influenced by the presence of periodontal lesions. This close link illustrates how an imbalance affecting one part of the body, in this case the tissues surrounding the teeth, can negatively influence the entire human body. Good health is a global state: even if our organs each have a well-defined role, their proper functioning remains strongly influenced by the general conditions prevailing throughout the body. This is particularly true with regard to inflammation, a condition that favours the development of all chronic diseases and which is responsible for the majority of deaths affecting the population. In this context, the increased risk of several diseases associated with periodontitis, especially cardiovascular disease, is not so surprising, since it essentially represents another example of the damage that can be caused by the presence of these chronic inflammatory conditions.

The close association between oral and cardiovascular health therefore suggests that the prevention and treatment of periodontitis may play important roles in the prevention of cardiovascular disease, particularly in those at higher risk due to being overweight, diabetes or a history of cardiovascular disease. This important link between the teeth and the rest of the body unfortunately remains under-exploited because medicine and dentistry are distinct disciplines, which have evolved in parallel, without much interaction between them. While one can be treated for free for all diseases that affect the body (in Canada), dental care does not benefit from this coverage and is therefore out of reach for those less well off. There is no doubt that this situation contributes to the high prevalence of periodontitis in our society and to the negative repercussions associated with these infections on health in general. Extending health insurance to cover dental care would therefore be an important step forward for cardiovascular prevention and the prevention of several other chronic diseases.

Childhood obesity, a ticking time bomb for cardiometabolic diseases

Childhood obesity, a ticking time bomb for cardiometabolic diseases

OVERVIEW

  • Obesity rates among Canadian children and teens have more than tripled over the past 40 years.
  • Childhood obesity is associated with a marked increase in the risk of type 2 diabetes and cardiovascular disease in adulthood, which can significantly reduce healthy life expectancy.
  • Policies to improve the diet of young people are key to reversing this trend and preventing an epidemic ofcardiometabolic diseases affecting young adults in the coming years.

One of the most dramatic changes to have occurred in recent years is undoubtedly the marked increase in the number of overweight children. For example, obesity rates among Canadian children and adolescents have more than tripled over the past 40 years. Whereas in 1975, obesity was a fairly rare problem affecting less than 3% of children aged 5–19, the prevalence of obesity has made a gigantic leap since that time, affecting nearly 14% of boys and 10% of girls in 2016 (Figure 1). If data on overweight is added to these figures, then approximately 25% of young Canadians are overweight (a similar trend is observed in Quebec). This prevalence of obesity appears to have plateaued in recent years, but recent US surveys suggest that the COVID-19 pandemic may have caused an upsurge in the number of overweight young people, particularly among 5-11-year-olds.

Figure 1. Increase in the prevalence of obesity among Canadian children over the past 40 years. From NCD Risk Factor Collaboration (2017).

Measuring childhood obesity
Although not perfect, the most common measure used to determine the presence of overweight in young people under the age of 19 is the body mass index (BMI), calculated by dividing the weight by the square of height (kg/m²). However, the values obtained must be adjusted according to age and sex to take into account changes in body composition during growth, as shown in Figure 2.

Figure 2. WHO growth standards for boys aged 5–19 living in Canada. Data comes from WHO (2007).

Note that a wide range of BMI on either side of the median (50th percentile) is considered normal. Overweight children have a BMI higher than that of 85–95% of the population of the same age (85th-95th percentile), while the BMI of obese children is higher than that of 97% of the population of the same age (97th percentile and above). Using z-scores is another way to visualize childhood overweight and obesity. This measurement expresses the deviation of the BMI from the mean value, in standard deviation. For example, a z-score of 1 means that the BMI is one standard deviation above normal (corresponding to overweight), while z-scores of 2 and 3 indicate, respectively, the presence of obesity and severe obesity.

This marked increase in the proportion of overweight children, and particularly obese children, is a worrying trend that bodes very badly for the health of future generations of adults. On the one hand, it is well established that obesity during childhood (and especially during adolescence) represents a very high risk factor for obesity in adulthood, with more than 80% of obese adults who were already obese during their childhood. This obesity in adulthood is associated with an increased risk of a host of health problems, both from a cardiovascular point of view (hypertension, dyslipidemia, ischemic diseases) and the development of metabolic abnormalities (hyperglycemia, resistance to insulin, type 2 diabetes) and certain types of cancer. Obesity can also cause discrimination and social stigma and therefore have devastating consequences on the quality of life, both physically and mentally.

Another very damaging aspect of childhood obesity, which is rarely mentioned, is the dramatic acceleration of the development of all the diseases associated with overweight. In other words, obese children are not only at higher risk of suffering from the various pathologies caused by obesity in adulthood, but these diseases can also affect them at an early age, sometimes even before reaching adulthood, and thus considerably reduce their healthy life expectancy. These early impacts of childhood obesity on the development of diseases associated with overweight are well illustrated by the results of several recent studies on type 2 diabetes and cardiovascular disease.

Early diabetes
Traditionally, type 2 diabetes was an extremely rare disease among young people (it was even called “adult diabetes” at one time), but its incidence has increased dramatically with the rise in the proportion of obese young people. For example, recent US statistics show that the prevalence of type 2 diabetes in children aged 10–19 has increased from 0.34 per 1000 children in 2001 to 0.67 in 2017, an increase of almost 100% since the beginning of the millennium.

The main risk factors for early diabetes are obesity, especially severe obesity (BMI greater than 35) or when the excess fat is mainly located in the abdomen, a family history of the disease, and belonging to certain ethnic groups. However, obesity remains the main risk factor for type 2 diabetes: in obese children (4–10 years) and adolescents (11–18 years), glucose intolerance is frequently observed during induced hyperglycemia tests, a phenomenon caused by the early development of insulin resistance. A characteristic of type 2 diabetes in young people is its rapid development. Whereas in adults, the transition from a prediabetic state to clearly defined diabetes is generally a gradual process, occurring over a period of 5–10 years, this transition can occur very quickly in young people, in less than 2 years. This means that the disease is much more aggressive in young people than in older people and can cause the early onset of various complications, particularly at the cardiovascular level.

A recent study, published in the prestigious New England Journal of Medicine, clearly illustrates the dangers that arise from early-onset type 2 diabetes, appearing during childhood or adolescence. In this study, the researchers recruited extremely obese children (BMI ≥ 35) who had been diagnosed with type 2 diabetes in adolescence and subsequently examined for ten years the evolution of different risk factors and pathologies associated with this disease.

The results are very worrying, because the vast majority of patients in the study developed one or more complications during follow-up that significantly increased their risk of developing serious health problems (Figure 3). Of particular note is the high incidence of hypertension, dyslipidemia (LDL-cholesterol and triglyceride levels too high), and kidney (nephropathies) and nerve damage (neuropathies) in this population, which, it should be remembered, is only 26 years on average. Worse still, almost a third of these young adults had 2 or more complications, which obviously increases the risk of deterioration of their health even more. Moreover, it should be noted that 17 serious cardiovascular accidents (infarction, heart failure, stroke) occurred during the follow-up period, which is abnormally high given the young age of the patients and the relatively small number of people who participated in the study (500 patients).

Figure 3. Incidence of different complications associated with type 2 diabetes in adolescents. From TODAY Study Group (2021).

It should also be noted that these complications occurred despite the fact that the majority of these patients were treated with antidiabetic drugs such as metformin or insulin. This is consistent with several studies showing that type 2 diabetes is much harder to control in young people than in middle-aged people. The mechanisms responsible for this difference are still poorly understood, but it seems that the development of insulin resistance and the deterioration of the pancreatic cells that produce this hormone progress much faster in young people than in older people, which complicates blood sugar control and increases the risk of complications.

This difficulty in effectively treating early type 2 diabetes means that young diabetics are much more at risk of dying prematurely than non-diabetics (Figure 4). For example, young people who develop early diabetes, before the age of 30, have a mortality rate 3 times higher than the population of the same age who is not diabetic. This increase remains significant, although less pronounced, until about age 50, while cases of diabetes that appear at older ages (60 years and over) do not have a major impact on mortality compared to the general population. It should be noted that this increase in mortality affecting the youngest diabetics is particularly pronounced at a young age, around 40 years of age.

These results therefore show how early type 2 diabetes can lead to a rapid deterioration in health and take decades off life, including years that are often considered the most productive of life (forties and fifties). For all these reasons, type 2 diabetes must be considered one of the main collateral damages of childhood obesity.

Figure 4. Age-standardized mortality rates for diagnosis of type 2 diabetes. Standardized mortality rates represent the ratio of mortality observed in individuals with diabetes to anticipated mortality for each age group. From Al-Saeed et al. (2016).

Cardiovascular disease
In recent years, there has been an upsurge in the incidence of cardiovascular disease in young adults. This new trend is surprising given that mortality from cardiovascular diseases has been in constant decline for several years in the general population (thanks in particular to a reduction in the number of smokers and improved treatments), and one might have expected that young people would also benefit from these positive developments.

The data collected so far strongly suggests that the increase in the prevalence of obesity among young people contributes to this upsurge of premature cardiovascular diseases, before the age of 55. On the one hand, it has been shown that a genetic predisposition to develop overweight during childhood is associated with an increased risk of coronary heart disease (and type 2 diabetes) in adulthood. On the other hand, this increased risk has also been observed in long-term studies examining the association between the weight of individuals during childhood and the incidence of cardiovascular events once they have reached adulthood. For example, a large Danish study of over 275,000 school-aged children (7–13 years old) showed that each one-unit increase in BMI z-score at these ages (see legend to Figure 2 for the definition of the z-score) was associated with an increased risk of cardiovascular disease in adulthood, after 25 years (Figure 5).

This increased risk is directly proportional to the age at which children are overweight, i.e., the more a high BMI is present at older ages, the greater the risk of suffering a cardiovascular event later in adulthood. For example, an increase of 1 in the z -score of 13-year-old children is associated with twice as much of an increase in risk in adulthood as a similar increase in a 7-year-old child (Figure 5). Similar results are observed for girls, but the increased risk of cardiovascular disease is lower than for boys.


Figure 5. Relationship between body mass index in childhood and the risk of cardiovascular disease in adulthood. The values represent the risks associated with a 1-unit increase in BMI z-score at each age. From Baker et al. (2007).

Early atherosclerosis
Several studies suggest that the increased risk of cardiovascular disease in adulthood observed in overweight children is a consequence of the early development of several risk factors that accelerate the process of atherosclerosis. Autopsy studies of obese adolescents who died of non-cardiovascular causes (e.g., accidents) revealed that fibrous atherosclerotic plaques were already present in the aorta and coronary arteries, indicating an abnormally rapid progression of atherosclerosis.

As mentioned earlier, type 2 diabetes is certainly the worst risk factor that can generate this premature progression, because the vast majority of diabetic children and adolescents very quickly develop several abnormalities that considerably increase the risk of serious damage to blood vessels (Figure 3). But even without the presence of early diabetes, studies show that several risk factors for cardiovascular disease are already present in overweight children, such as hypertension, dyslipidemia, chronic inflammation, glucose intolerance or even vascular abnormalities (thickening of the internal wall of the carotid artery, for example). Exposure to these factors that begins in childhood therefore creates favourable conditions for the premature development of atherosclerosis, thereby increasing the risk of cardiovascular events in adulthood.

It should be noted, however, that the negative impact of childhood obesity on health in adulthood is not irreversible. Indeed, studies show that people who were overweight or obese during childhood, but who had a normal weight in adulthood, have a risk of cardiovascular disease similar to that of people who have been thin all their lives. However, obesity is extremely difficult to treat, both in childhood and in adulthood, and the best way to avoid prolonged chronic exposure to excess fat and damage to cardiovascular health (and health in general) which results from it is obviously to prevent the problem at the source by modifying lifestyle factors, which are closely associated with an increased risk of developing overweight, in particular the nature of the diet and physical activity (psychosocial stress may also play a role). Given the catastrophic effects of childhood obesity on health, cardiovascular health in particular, the potential for this early preventive approach (called “primordial prevention”) is immense and could help halt the current rise in diabetes and premature mortality affecting young adults.

Ideal cardiovascular health
A recent study shows how this primordial prevention approach can have an extraordinary impact on cardiovascular health. In this study, researchers determined the ideal cardiovascular health score, as defined by the American Heart Association (Table 1), of more than 3 million South Koreans with an average age of 20–39 years. Excess weight is a very important element of this score because of its influence on other risk factors also used in the score such as hypertension, fasting hyperglycemia and cholesterol.

Participants were followed for a period of approximately 16 years, and the incidence of premature cardiovascular disease (before age 55) was assessed using as the primary endpoint a combination of hospitalization for infarction, stroke, cardiac insufficiency, or sudden cardiac death.

Table 1. Parameters used to define the ideal cardiovascular health score. Since there is 1 point for each target reached, a score of 6 reflects optimal cardiovascular health. Adapted from Lloyd-Jones et al. (2010), excluding dietary factors that were not assessed in the Korean study.

As shown in Figure 6, cardiovascular health in early adulthood has a decisive influence on the risk of cardiovascular events that occur prematurely, before the age of 55. Compared to participants in very poor cardiovascular health at the start (score of 0), each additional target reached reduces the risk of cardiovascular events, with maximum protection of approximately 85% in people whose lifestyle allows achieving 5 or more ideal heart health targets (scores of 5 and 6). Similar results were obtained in the United States and show how early health, from childhood through young adulthood, plays a key role in preventing the development of cardiovascular disease during aging.

Figure 6. Influence of cardiovascular health in young adults on the risk of premature cardiovascular events. From Lee et al. (2021).

Yet our society remains strangely passive in the face of the rise in childhood obesity, as if the increase in body weight of children and adolescents has become the norm and that nothing can be done to reverse this trend. This lack of interest is really difficult to understand, because the current situation is a ticking time bomb that risks causing a tsunami of premature chronic diseases in the near future, affecting young adults. This is an extremely worrying scenario if we consider that our healthcare system, in addition to having to contend with diseases that affect an aging population (1 out of 4 Quebecers will be over 65 in 2030), will also have to deal with younger patients suffering from cardiometabolic diseases caused by overweight. Needless to say, this will be a significant burden on healthcare systems.

This situation is not inevitable, however, as governments have concrete legislative means that can be used to try to reverse this trend. Several policies aimed at improving diet quality to prevent disease can be quickly implemented:

  • Taxing sugary drinks. A simple and straightforward approach that has been adopted by several countries is to introduce a tax on industrial food products, especially soft drinks. The principle is the same as for all taxes affecting other products harmful to health such as alcohol and tobacco, i.e., an increase in prices is generally associated with a reduction in consumption. Studies that have examined the impact of this approach for soft drinks indicate that this is indeed the case, with reductions in consumption observed (among others) in Mexico, Berkeley (California) and Barbados. This approach therefore represents a promising tool, especially if the amounts collected are reinvested in order to improve the diet of the population (subsidies for the purchase of fruit and vegetables, for example).
  • Requiring clear nutrition labels on packaging. We can help consumers make informed choices by clearly indicating on the front of the product whether it is high in sugar, fat or salt, as is the case in Chile (see our article on this subject).
  • Eliminating the marketing of unhealthy foods for children. The example of Chile also shows that severe restrictions can be imposed on the marketing of junk food products by prohibiting the advertising of these products in programs or websites aimed at young people as well as by prohibiting their sale in schools. The United Kingdom plans to take such an approach very soon by eliminating all advertising online and on television of products high in sugar, salt and fat before 9 p.m., while Mexico has gone even further by banning all sales of junk food products to children.

There is no reason Canada should not adopt such approaches to protect the health of young people.

Lignans: Compounds of plant origin that promote good cardiovascular health

Lignans: Compounds of plant origin that promote good cardiovascular health

OVERVIEW

  • Dietary lignans are phenolic compounds that come mainly from plant-based foods, especially seeds, whole grains, fruits, vegetables, wine, tea and coffee.
  • Consumption of lignans is associated with a reduced risk of developing cardiovascular disease, according to several well-conducted studies.

There are over 8,000 phenolic and polyphenolic compounds found in plants. These compounds are not nutrients, but they have various beneficial biological activities in the human body. They are generally grouped into 4 classes: phenolic acids, flavonoids, stilbenes (e.g., resveratrol), and lignans. Lignans are dimers of monolignols, which can also be used in the synthesis of a long branched polymer, lignin, found in the walls of the conductive vessels of plants. From a nutritional standpoint, lignins are considered to be a component of insoluble dietary fibre.

Figure 1. Structures of the main dietary lignans

Dietary lignans, the most important of which are matairesinol, secoisolariciresinol, pinoresinol and lariciresinol, come mainly from plant-based foods, particularly seeds, whole grains, fruits, vegetables, wine, tea and coffee (see Table 1). Other lignans are found only in certain types of food, such as medioresinol (sesame seeds, rye, lemon), syringaresinol (grains), sesamin (sesame seeds). Lignans are converted into enterolignans by the gut microbiota, which are then absorbed into the bloodstream and distributed throughout the body.

Table 1. Lignan content of commonly consumed foods.
Adapted from Peterson et al., 2010 and Rodriguez-Garcia et al., 2019.

Several studies indicate that lignans can prevent cardiovascular disease and other chronic diseases, including cancer, and improve cardiovascular health, through its anti-inflammatory and estrogenic properties (the ability to bind to estrogen receptors).

A recently published US study indicates that there is a significant association between dietary intake of lignans and the incidence of coronary heart disease. Among the 214,108 people from 3 cohorts of healthcare professionals, those who consumed the most lignans (total) had a 15% lower risk of developing coronary heart disease than those who consumed little. Considering each lignan separately, the association was particularly favourable for matairesinol (-24%), compared to secoisolariciresinol (-13%), pinoresinol (-11%), and lariciresinol (-11%). There is a nonlinear dose-response relationship for total lignans, matairesinol, and secoisolariciresinol with a plateau (maximum effect) at approximately 300 µg/day, 10 µg/day, and 100 µg/day, respectively. Canadians consume an average of 857 µg of lignans per day, enough to benefit from the positive effects on cardiovascular health, but residents of some Western countries such as the United Kingdom, the United States and Germany do not have an optimal intake of lignans (Table 2).

The favourable association for lignans was especially apparent among participants who had a high dietary fibre intake. The authors of the study suggest that fibre, by supporting a healthy microbiota, may promote the production of enterolignans in the gut.

Table 2. Daily intake of lignans in Western countries.
Adapted from Peterson et al., 2010.

PREDIMED (Prevención con Dieta Mediterránea), a recognized study conducted among over 7,000 Spaniards (55–80 years old) at high risk of developing cardiovascular disease, compared the Mediterranean diet (supplemented with nuts and extra virgin olive) to a low-fat diet advocated by the American Heart Association for the prevention of cardiovascular disease (CVD). In this study, the Mediterranean diet was clearly superior to the low-fat diet in preventing CVD, so the study was stopped after 4.8 years for ethical reasons. Further analysis of the PREDIMED data showed that there is a very favourable association between a high dietary intake of polyphenols and the risk of CVD. Participants who consumed the most total polyphenols had a 46% lower risk of CVD than those who consumed the least. The polyphenols that were most strongly associated with reduced risk of CVD were flavanols (-60%), hydroxybenzoic acids (-53%), and lignans (-49%). It should be noted that the nuts and extra virgin olive oil that were consumed daily by participants in the PREDIMED study contain appreciable amounts of lignans.

Another analysis  of data from the PREDIMED study showed a favourable association between total polyphenol intake and the risk of death from any cause. A high intake of total polyphenols, compared to a low intake, was associated with a 37% reduction in the risk of premature mortality. Stilbenes and lignans were the most favourable polyphenols for reducing the risk of mortality, by 52% and 40%, respectively. In this case, flavonoids and phenolic acids were not associated with a significant reduction in mortality risk.

No randomized controlled studies on phenolic compounds and the risk of CVD have been performed to date. There is therefore no direct evidence that lignans protect the cardiovascular system, but all the data from population studies suggests that it is beneficial for health to increase the dietary intake of lignans and therefore to eat more fruits, vegetables, whole grains, legumes, nuts and extra virgin olive oil, which are excellent sources of these still too little known plant-based compounds.

Choosing the right sources of carbohydrates is essential for preventing cardiovascular disease

Choosing the right sources of carbohydrates is essential for preventing cardiovascular disease

OVERVIEW

  • Recent studies show that people who regularly consume foods containing low-quality carbohydrates (simple sugars, refined flours) have an increased risk of cardiovascular events and premature mortality.
  • Conversely, a high dietary intake of complex carbohydrates, such as resistant starches and dietary fibre, is associated with a lower risk of cardiovascular disease and improved overall health.
  • Favouring the regular consumption of foods rich in complex carbohydrates (whole grains, legumes, nuts, fruits and vegetables) while reducing that of foods containing simple carbohydrates (processed foods, sugary drinks, etc.) is therefore a simple way to improve cardiovascular health.

It is now well established that a good quality diet is essential for the prevention of cardiovascular disease and the maintenance of good health in general. This link is particularly well documented with regard to dietary fat: several epidemiological studies have indeed reported that too high a dietary intake of saturated fat increases LDL cholesterol levels, an important contributor to the development of atherosclerosis, and is associated with an increased risk of cardiovascular disease. As a result, most experts agree that we should limit the intake of foods containing significant amounts of saturated fat, such as red meat, and instead focus on sources of unsaturated fat, such as vegetable oils (especially extra virgin olive oil and those rich in omega-3s such as canola), as well as nuts, certain seeds (flax, chia, hemp) and fish (see our article on this subject). This roughly corresponds to the Mediterranean diet, a diet that has repeatedly been associated with a lower risk of several chronic diseases, especially cardiovascular disease.

On the carbohydrate side, the consensus that has emerged in recent years is to favour sources of complex carbohydrates such as whole grains, legumes and plants in general while reducing the intake of simple carbohydrates from refined flour and added sugars. Following this recommendation, however, can be much more difficult than one might think, as many available food products contain these low-quality carbohydrates, especially the entire range of ultra-processed products, which account for almost half of the calories consumed by the population. It is therefore very important to learn to distinguish between good and bad carbohydrates, especially since these nutrients are the main source of calories consumed daily by the majority of people. To achieve this, we believe it is useful to recall where carbohydrates come from and how industrial processing of foods can affect their properties and impacts on health.

Sugar polymers
All of the carbohydrates in our diet come from, in one way or another, plants. During the photosynthetic reaction, in addition to forming oxygen (O2) from carbon dioxide in the air (CO2), plants also simultaneously transform the energy contained in solar radiation into chemical energy, in the form of sugar:

6 CO2 + 12 H2O + light → C6H12O6 (glucose) + 6 O2 + 6 H2O

In the vast majority of cases, this sugar made by plants does not remain in this simple sugar form, but is rather used to make complex polymers, i.e., chains containing several hundred (and in some cases thousands) sugar molecules chemically bonded to one another. An important consequence of this arrangement is that the sugar contained in these complex carbohydrates is not immediately accessible and must be extracted by digestion before reaching the bloodstream and serving as a source of energy for the body’s cells. This prerequisite helps prevent sugar from entering the blood too rapidly, which would unbalance the control systems responsible for maintaining the concentration of this molecule at levels just sufficient enough to meet the needs of the body. And these levels are much lower than one might think; on average, the blood of a healthy person contains a maximum of 4 to 5 g of sugar in total, or barely the equivalent of a teaspoon. Dietary intake of complex carbohydrates therefore provides enough energy to support our metabolism, while avoiding excessive fluctuations in blood sugar that could lead to health problems.

Figure 1 illustrates the distribution of the two main types of sugar polymers in the plant cell: starches and fibres.

Figure 1. The physicochemical characteristics and physiological impacts of starches and dietary fibres from plant cells. Adapted from Gill et al. (2021).

Starches. Starches are glucose polymers that the plant stores as an energy reserve in granules (amyloplasts) located inside plant cells. This source of dietary carbohydrates has been part of the human diet since the dawn of time, as evidenced by the recent discovery of genes from bacteria specializing in the digestion of starches in the dental plaque of individuals of the genus Homo who lived more than 100,000 years ago. Even today, a very large number of plants commonly eaten are rich in starch, in particular tubers (potatoes, etc.), cereals (wheat, rice, barley, corn, etc.), pseudocereals (quinoa, chia, etc.), legumes, and fruits.

Digestion of the starches present in these plants releases units of glucose into the bloodstream and thus provides the energy necessary to support cell metabolism. However, several factors can influence the degree and speed of digestion of these starches (and the resulting rise in blood sugar). This is particularly the case with “resistant starches” which are not at all (or very little) digested during gastrointestinal transit and therefore remain intact until they reach the colon. Depending on the factors responsible for their resistance to digestion, three main types of these resistant starches (RS) can be identified:

  • RS-1: These starches are physically inaccessible for digestion because they are trapped inside unbroken plant cells, such as whole grains.
  • RS-2: The sensitivity of starches to digestion can also vary considerably depending on the source and the degree of organization of the glucose chains within the granules. For example, the most common form of starch in the plant kingdom is amylopectin (70–80% of total starch), a polymer made up of several branches of glucose chains. This branched structure increases the contact surface with enzymes specialized in the digestion of starches (amylases) and allows better extraction of the glucose units present in the polymer. The other constituent of starch, amylose, has a much more linear structure which reduces the efficiency of enzymes to extract the glucose present in the polymer. As a result, foods with a higher proportion of amylose are more resistant to breakdown, release less glucose, and therefore cause lower blood sugar levels. This is the case, for example, with legumes, which contain up to 50% of their starch in the form of amylose, which is much more than other commonly consumed sources of starches, such as tubers and grains.
  • RS-3: These resistant starches are formed when starch granules are heated and subsequently cooled. The resulting starch crystallization, a phenomenon called retrogradation, creates a rigid structure that protects the starch from digestive enzymes. Pasta salads, potato salads, and sushi rice are all examples of foods containing resistant starches of this type.

An immediate consequence of this resistance of digestion-resistant starches is that these glucose polymers can be considered dietary fibre from a functional point of view. This is important because, as discussed below, the fermentation of fibre by the hundreds of billions of bacteria (microbiota) present in the colon generates several metabolites that play extremely important roles in the maintenance of good health.

Dietary fibre. Fibres are polymers of glucose present in large quantities in the wall of plant cells where they play an important role in maintaining the structure and rigidity of plants. The structure of these fibres makes them completely resistant to digestion and the sugar they contain does not contribute to energy supply. Traditionally, there are two main types of dietary fibre, soluble and insoluble, each with its own physicochemical properties and physiological effects. Everyone has heard of insoluble fibre (in wheat bran, for example), which increases stool volume and speeds up gastrointestinal transit (the famous “regularity”). This mechanical role of insoluble fibres is important, but from a physiological point of view, it is mainly soluble fibres that deserve special attention because of the many positive effects they have on health.

By capturing water, these soluble fibres increase the viscosity of the digestive contents, which helps to reduce the absorption of sugar and dietary fats and thus to avoid excessive increases in blood sugar and blood lipid levels that can contribute to atherosclerosis (LDL cholesterol, triglycerides). The presence of soluble fibre also slows down gastric emptying and can therefore decrease calorie intake by increasing feelings of satiety. Finally, the bacterial community that resides in the colon (the microbiota) loves soluble fibres (and resistant starches), and this bacterial fermentation generates several bioactive substances, in particular the short chain fatty acids (SCFA) acetate, propionate and butyrate. Several studies carried out in recent years have shown that these molecules exert a myriad of positive effects on the body, whether by reducing chronic inflammation, improving insulin resistance, lowering blood pressure and the risk of cardiovascular disease, or promoting the establishment of a diversified microbiota, optimal for colon health (Table 1).

A compilation of many studies carried out in recent years (185 observational studies and 58 randomized trials, which equates to 135 million person-years) indicates that consuming 25 to 30 g of fibre per day seems optimal to benefit from these protective effects, approximately double the current average consumption.

Table 1. Main physiological effects of dietary fibre. Adapted from Barber (2020).

Physiological effectsBeneficial health impacts
MetabolismImproved insulin sensitivity
Reduced risk of type 2 diabetes
Improved blood sugar and lipid profile
Body weight control
Gut microbiotaPromotes a diversified microbiota
Production of short-chain fatty acids
Cardiovascular systemDecrease in chronic inflammation
Reduced risk of cardiovascular events
Reduction of cardiovascular mortality
Digestive systemDecreased risk of colorectal cancer

Overall, we can therefore see that the consumption of complex carbohydrates is optimal for our metabolism, not only because it ensures an adequate supply of energy in the form of sugar, without causing large fluctuations in blood sugar, but also because it provides the intestinal microbiota with the elements necessary for the production of metabolites essential for the prevention of several chronic diseases and for the maintenance of good health in general.

Modern sugars
The situation is quite different, however, for several sources of carbohydrates in modern diets, especially those found in processed industrial foods. Three main problems are associated with processing:

Simple sugars. Simple sugars (glucose, fructose, galactose, etc.) are the molecules responsible for the sweet taste: the interaction of these sugars with receptors present in the tongue sends a signal to the brain warning it of the presence of an energy source. The brain, which alone consumes no less than 120 g of sugar per day, loves sugar and responds positively to this information, which explains our innate attraction to foods with a sweet taste. On the other hand, since the vast majority of carbohydrates produced by plants are in the form of polymers (starches and fibres), simple sugars are actually quite rare in nature, being mainly found in fruits, vegetables such as beets, or even some grasses (sugar cane). It is therefore only with the industrial production of sugar from sugar cane and beets that consumers’ “sweet tooth” could be satisfied on a large scale and that simple sugars became commonly consumed. For example, data collected in the United States shows that between 1820 and 2016, the intake of simple sugars increased from 6 lb (2.7 kg) to 95 lb (43 kg) per person per year, an increase of about 15 times in just under 200 years (Figure 2).

 

 

Figure 2. Consumption of simple sugars in the United States between 1820 and 2016.  From Guyenet (2018).

Our metabolism is obviously not adapted to this very high intake of simple sugars, far beyond what is normally found in nature. Unlike the sugars found in complex carbohydrates, these simple sugars are absorbed very quickly into the bloodstream and cause very rapid and significant increases in blood sugar. Several studies have shown that people who frequently consume foods containing these simple sugars are more likely to suffer from obesity, type 2 diabetes and cardiovascular disease. For example, studies have found that consuming 2 servings of sugary drinks daily was associated with a 35% increase in the risk of coronary heart disease. When the amount of added sugars consumed represents 25% of daily calories, the risk of heart disease nearly triples. Factors that contribute to this detrimental effect of simple sugars on cardiovascular health include increased blood pressure and triglyceride levels, lowered HDL cholesterol, and increased LDL cholesterol (specifically small, very dense LDLs, which are more harmful to the arteries), as well as an increase in inflammation and oxidative stress.

It is therefore necessary to restrict as much as possible the intake of simple sugars, which should not exceed 10% of the daily energy intake according to the World Health Organization. For the average adult who consumes 2,000 calories per day, that’s just 200 calories, or about 12 teaspoons of sugar or the equivalent of a single can of soft drink.

Refined flour.  Cereals are a major source of carbohydrates (and calories) in most food cultures around the world. When they are in whole form, i.e., they retain the outer shell rich in fibre and the germ containing several vitamins and minerals, cereals are a source of complex carbohydrates (starches) of high quality and beneficial to health. This positive impact of whole grains is well illustrated by the reduced risk of coronary heart disease and mortality observed in a large number of population studies. For example, recent meta-analyses have shown that the consumption of about 50 g of whole grains perday is associated with a 22–30% reduction in cardiovascular disease mortality, a 14–18% reduction in cancer-relatedmortality, and a 19–22% reduction in total mortality.

On the other hand, these positive effects are completely eliminated when the grains are refined with modern industrial metal mills to produce the flour used in the manufacture of a very large number of commonly consumed products (breads, pastries, pasta, desserts, etc.). By removing the outer shell of the grain and its germ, this process improves the texture and shelf life of the flour (the unsaturated fatty acids in the germ are sensitive to rancidity), but at the cost of the almost total elimination of fibres and a marked depletion of several nutrients (minerals, vitamins, unsaturated fatty acids, etc.). Refined flours therefore essentially only contain sugar in the form of starch, this sugar being much easier to assimilate due to the absence of fibres that normally slow down the digestion of starch and the absorption of released sugar (Figure 3).

Figure 3. Schematic representation of a whole and refined grain of wheat.

Fibre deficiency. Fortification processes partially compensate for the losses of certain nutrients (e.g., folic acid) that occur during the refining of cereal grains. On the other hand, the loss of fibre during grain refining is irreversible and is directly responsible for one of the most serious modern dietary deficiencies given the many positive effects of fibre on the prevention of several chronic diseases.

Poor-quality carbohydrates
Low-quality carbohydrate sources with a negative impact on health are therefore foods containing a high amount of simple sugars, having a higher content of refined grains than whole grains, or containing a low amount of fibre (or several of these characteristics simultaneously). A common way to describe these poor-quality carbohydrates is to compare the rise in blood sugar they produce to that of pure glucose, called the glycemic index (GI) (see box). The consumption of food with a high glycemic index causes a rapid and dramatic rise in blood sugar levels, which causes the pancreas to secrete a large amount of insulin to get glucose into the cells. This hyperinsulinemia can cause glucose to drop to too low levels, and the resulting hypoglycemia can ironically stimulate appetite, despite ingesting a large amount of sugar a few hours earlier. Conversely, a food with a low glycemic index produces lower, but sustained, blood sugar levels, which reduces the demand for insulin and helps prevent the fluctuations in blood glucose levels often seen with foods with a high glycemic index. Potatoes, breakfast cereals, white bread, and pastries are all examples of high glycemic index foods, while legumes, vegetables, and nuts are conversely foods with a low glycemic index.

Glycemic index and load
The glycemic index (GI) is calculated by comparing the increase in blood sugar levels produced by the absorption of a given food with that of pure glucose. For example, a food that has a glycemic index of 50 (lentils, for example) produces a blood sugar half as important as glucose (which has a glycemic index of 100). As a general rule, values below 50 are considered to correspond to a low GI, while those above 70 are considered high. The glycemic index, however, does not take into account the amount of carbohydrate in foods, so it is often more appropriate to use the concept of glycemic load (GL). For example, although watermelon and breakfast cereals both have high GIs (75), the low-carbohydrate content of melon (11 g per 100 g) equates to a glycemic load of 8, while 26 g of carbohydrates present in breakfast cereals result in a load of 22, which is three times more. GLs ≥ 20 are considered high, intermediate when between 11 and 19, and low when ≤ 10.

PURE study
Results from the PURE (Prospective Urban and Rural Epidemiology) epidemiological study conducted by Canadian cardiologist Salim Yusuf have confirmed the link between low-quality carbohydrates and the risk of cardiovascular disease. In the first of these studies, published in the prestigious New England Journal of Medicine, researchers examined the association between the glycemic index and the total glycemic load of the diet and the incidence of major cardiovascular events (heart attack, stroke, sudden death, heart failure) in more than 130,000 participants aged 35 to 70, spread across all five continents. The study finds that a diet with a high glycemic index is associated with a significant (25%) increase in the risk of having a major cardiovascular event in people without cardiovascular disease, an increase that reaches 51% in those with pre-existing cardiovascular disease (Figure 4). A similar trend is observed for the glycemic load, but in the latter case, the increased risk seems to affect only those with cardiovascular disease at the start of the study.

Figure 4. Comparison of the risk of cardiovascular events according to the glycemic index or the glycemic load of the diet of healthy people (blue) or with a history of cardiovascular disease (red). The median glycemic index values were 76 for quintile 1 and 91 for quintile 5. For glycemic load, the mean values were 136 g of carbohydrates per day for Q1 and 468 g per day for Q5. Note that the increased risk of cardiovascular events associated with a high glycemic index or load is primarily seen in participants with pre-existing cardiovascular disease. From Jenkins et al. (2021).

The impact of the glycemic index appears to be particularly pronounced in overweight people (Figure 5). Thus, while the increase in the risk of major cardiovascular events is 14% in thin people with a BMI less than 25, it reaches 38% in those who are overweight (BMI over 25).

 

Figure 5. Impact of overweight on the increased risk of cardiovascular events related to the glycemic index of the diet. The values shown represent the increased risk of cardiovascular events observed for each category (quintiles 2 to 5) of the glycemic index compared to the category with the lowest index (quintile 1). The median values of the glycemic indices were 76 for quintile 1; 81 for quintile 2; 86 for quintile 3; 89 for quintile 4; and 91 for quintile 5. Taken from Jenkins et al. (2021).

This result is not so surprising, since it has long been known that excess fat disrupts sugar metabolism, especially by producing insulin resistance. A diet with a high glycemic index therefore exacerbates the rise in postprandial blood sugar already in place due to excess weight, which leads to a greater increase in the risk of cardiovascular disease. The message to be drawn from this study is therefore very clear: a diet containing too many easily assimilated sugars, as measured using the glycemic index, is associated with a significant increase in the risk of suffering a major cardiovascular event. The risk of these events is particularly pronounced for people with less than optimal health, either due to the presence of excess fat or pre-existing cardiovascular disease (or both). Reducing the glycemic index of the diet by consuming more foods containing complex carbohydrates (fruits, vegetables, legumes, nuts) and fewer products containing added sugars or refined flour is therefore an essential prerequisite for preventing the development of cardiovascular disease.

Refined flours
Another part of the PURE study looked more specifically at refined flours as a source of easily assimilated sugars that can abnormally increase blood sugar levels and increase the risk of cardiovascular disease. Researchers observed that a high intake (350 g per day, or 7 servings) of products containing refined flours (white bread, breakfast cereals, cookies, crackers, pastries) was associated with a 33% increase in the risk of coronary heart disease, 47% in the risk of stroke, and 27% in the risk of premature death. These observations therefore confirm the negative impact of refined flours on health and the importance of including as much as possible foods containing whole grains in the diet. The preventive potential of this simple dietary change is enormous since the consumption of whole grains remains extremely low, with the majority of the population of industrialized countries consuming less than 1 serving of whole grains daily, well below the recommended minimum (half of all grain products consumed, or about 5 servings per day).

Wholemeal breads are still a great way to boost the whole-grain intake. However, special attention must be paid to the list of ingredients. In Canada, the law allows up to 5% of the grain to be removed when making whole wheat flour, and the part removed contains most of the germ and a fraction of the bran (fibres). This type of bread is superior to white bread, but it is preferable to choose products made from whole-grain flour which contains all the parts of the grain. Note also that multigrain breads (7-14 grains) always contain 80% wheat flour and a maximum of 20% of a mixture of other grains (otherwise the bread does not rise), so the number of grains does not matter, but what does matter is whether the flour is whole wheat or ideally integral, which is not always the case.

In short, a simple way to reduce the risk of cardiovascular events and improve health in general is to replace as much as possible the intake of foods rich in simple sugars and refined flour with plant-based foods containing complex carbohydrates. In addition to carbohydrates, this simple change alone will influence the nature of the proteins and lipids ingested as well as, at the same time, all the phenomena that promote the appearance and progression of atherosclerotic plaques.

Omega-3 fatty acid supplements are ineffective for the prevention of cardiovascular disease

Omega-3 fatty acid supplements are ineffective for the prevention of cardiovascular disease

OVERVIEW

  • The VITAL study in participants who did not have cardiovascular disease and the ASCEND study in diabetic patients did not show a beneficial effect of omega-3 fatty acid supplements on cardiovascular health.
  • The REDUCE-IT study reported a beneficial effect of an omega-3 fatty acid supplement (Vascepa®), while the STRENGTH study reported no effect of another supplement (Epanova®).
  • The divergent results of the REDUCE-IT and STRENGTH studies have raised scientific controversy, mainly about the questionable use of mineral oil as a neutral placebo in the REDUCE-IT study.
  • Overall, the results of the studies lead to the conclusion that omega-3 fatty acid supplements are ineffective in preventing cardiovascular disease, in primary prevention and most likely also in secondary prevention.

Consuming fish on a regular basis (1–2 times per week) is associated with a reduced risk of death from coronary heart disease (see these meta-analyses here and here). In addition, favourable associations between fish consumption and the risks of type 2 diabetes, stroke, dementia, Alzheimer’s disease and cognitive decline have also been identified.

A large number of studies have suggested that it is mainly omega-3 (O-3) fatty acids, a type of very long-chain polyunsaturated fatty acid found in high amounts in several fish species, that are the cause of the positive health effects of eating fish and other seafood. For example, a meta-analysis of 17 prospective studies published in 2021 indicates that the risk of dying prematurely was significantly lower (15–18%) in participants who had the most circulating O-3s, compared to those who had the least. In addition, favourable associations of the same magnitude were observed for cardiovascular and cancer-related mortality.

Since eating fish is associated with better cardiovascular health, why not isolate the “active ingredient”, i.e. the omega-3 fatty acids it contains and make supplements with them? This seemed like a great idea; the same pharmacological approach has been applied successfully to a host of plants, fungi and microorganisms, which has made it possible to create drugs. One such example is aspirin, a derivative of salicylic acid found in the bark of certain tree species, quinine extracted from the cinchona shrub (antimalarial), digitoxin extracted from purple digitalis (treatment of heart problems), paclitaxel from yew (anticancer), etc.

Are marine O-3 supplements just as or even more effective than the whole food from which they are extracted? Several randomized controlled studies (RCTs) have been carried out in recent years to try to prove the effectiveness of O-3s. Meta-analyses of RCTs (see here and here) indicate that O-3 supplements (EPA and DHA) have little or no effect in primary prevention, i.e. on the risk of developing cardiovascular disease or dying prematurely from cardiovascular disease or any other cause. In contrast, data from some studies indicated that O-3 supplements may have beneficial effects in secondary prevention, i.e. in people with cardiovascular disease.

In order to obtain a higher level of evidence, several large, well-planned and controlled studies have been carried out recently: ASCEND, VITAL, STRENGTH and REDUCE-IT. The VITAL study (VITamin D and omegA-3 TriaL) in 25,871 participants who did not have cardiovascular disease and the ASCEND study (A Study of Cardiovascular Events in Diabetes) in 15,480 diabetic patients did not demonstrate any beneficial effects of O-3 supplements on cardiovascular health.

The results of the REDUCE-IT (REDUction of Cardiovascular Events with Icosapent ethyl-Intervention Trial) and STRENGTH (Outcomes Study to Assess STatin Residual Risk Reduction With EpaNova in HiGh CV Risk PatienTs With Hypertriglyceridemia) studies were then published. The results of these studies were eagerly anticipated since they tested the effect of O-3 supplements on major strokes at high doses (3000–4000 mg O-3/day) in patients at risk treated with a statin to lower blood cholesterol, but who had high triglyceride levels.

The results of these two studies are divergent, which has raised scientific controversy. The REDUCE-IT study reported a significant reduction of 25% in the number of cardiovascular events in the group of patients who took daily O-3 supplementation (Vascepa®; ethyl-EPA), compared to the group of patients who took a placebo (mineral oil). The STRENGTH study reported an absence of effect of O-3 supplements (Epanova®; a mixture of EPA and DHA in the form of carboxylic acids) on major cardiovascular events in patients treated with a statin, compared to the group of patients who took a corn oil placebo.

Several hypotheses have been proposed to explain the different results between the two large studies. One of them is that the mineral oil used as a placebo in the REDUCE-IT study may have caused adverse effects that would have led to a false positive effect of the O-3 supplement. Indeed, mineral oil is not a neutral placebo since it caused an average increase of 37% of C-reactive protein (CRP), a marker of systemic inflammation in the control group, as well as a 7.4% increase in LDL cholesterol and 6.7% in apolipoprotein B compared to the group that took Vascepa. These three biomarkers are associated with an increased risk of cardiovascular events.

Two other hypotheses could explain the difference between the two studies. It is possible that the moderately higher plasma levels of EPA obtained in the REDUCE-IT study could be the cause of the beneficial effects seen in this study, or that the DHA used in combination with EPA in the STRENGTH study may have counteracted the beneficial effects of EPA.

To test these two hypotheses, the researchers responsible for the STRENGTH study performed post-hoc analyses of the data collected during their clinical trial. Patients were classified according to their plasma EPA level after 12 months of daily supplementation with O-3. Thus, in the first tertile, patients had an average plasma EPA concentration of 30 µg/mL, those in the second tertile: 90 µg/mL, and those in the third tertile: 151 µg/mL. The mean plasma concentration of EPA in the third tertile (151 µg/mL) is comparable to that reported in the REDUCE-IT study (144 µg/mL). Analyses show that there was no association between the plasma concentration of EPA or DHA and the number of major cardiovascular events. The authors conclude that there is no benefit to taking O-3 supplements for secondary prevention, but they suggest that more studies should be done in the future to compare mineral oil and corn oil as placebos and also to compare different formulations of omega-3 fatty acids.

Overall, the results of recent studies lead to the conclusion that O-3 supplements are ineffective in preventing cardiovascular disease, in primary prevention and most likely also in secondary prevention. It should be noted that, taken in large amounts, O-3 supplements can have unwanted effects. In fact, in both the STRENGTH and REDUCE-IT studies, the incidence of atrial fibrillation was significantly higher with the use of O-3 supplements. In addition, bleeding was more common in patients who took ethyl-EPA (Vascepa®) in the REDUCE-IT study than in patients who took the placebo. It therefore seems safer to eat fish once or twice a week to maintain good health than to take ineffective and expensive supplements.