The benefits of extra virgin olive oil on cardiovascular health

The benefits of extra virgin olive oil on cardiovascular health

OVERVIEW

  • In addition to being an excellent source of monounsaturated fat, olive oil is the only vegetable oil that contains a significant amount of phenolic compounds with antioxidant and anti-inflammatory properties.
  • These molecules are found in much larger quantities in extra virgin quality oils compared to refined olive oils.
  • Several studies indicate that the presence of these phenolic compounds contributes to the many positive effects of extra virgin olive oil on cardiovascular health.

The traditional Mediterranean diet has several positive effects on cardiovascular health by improving the lipid profile (cholesterol, triglycerides) and by reducing chronic inflammation, blood pressure, blood sugar and the risk of diabetes. Several studies have clearly established that these effects result in a significant reduction in the risk of cardiovascular disease.

The Mediterranean diet is characterized by the abundant consumption of plant-based foods (fruits, vegetables, whole-grain cereals, legumes, nuts, herbs), a moderate intake of fermented dairy products (yogurt, cheese), fish, seafood and red wine as well as a low consumption of red meat and added sugars. It is therefore an exemplary diet, in which complex plant sugars are the main sources of carbohydrates and where the proteins come mainly from fish and legumes instead of red meat.

Another important feature of the Mediterranean diet is the daily use of large amounts (60–80 mL) of olive oil as the main source of fat for cooking. Several studies have reported that countries that are heavy consumers of olive oil have a much lower incidence of cardiovascular disease than those that consume mainly animal fats, suggesting a positive role of olive oil in this protective effect. Traditionally, these beneficial properties of olive oil have been attributed to its very high content (around 80%) of oleic acid, a monounsaturated fatty acid that contributes to its antioxidant properties. However, and unlike most vegetable oils, olive oil also contains a host of minor compounds (1–3% of the oil) that also play very important roles in its positive effects on cardiovascular health (see below). This is particularly the case for several phenolic compounds found exclusively in olive oil, including phenolic alcohols such as hydroxytyrosol and tyrosol and polyphenols of the secoiridoid family such as oleuropein, ligstroside, oleacein and oleocanthal (Figure 1).

 

Figure 1. Molecular structures of the main phenolic compounds of olive oil.


One fruit, several types of oils
Most vegetable oils come from seeds that have been extracted with an organic solvent (e.g. hexane) and subsequently heated to a high temperature to evaporate this solvent and remove impurities that give them an undesirable smell and flavour. These drastic procedures are not necessary for olive oil as the olives are simply pressed and the oil in the pulp is extracted by mechanical pressure, without using chemical processes or excessive heat.

Olive oils are classified according to the quality of the oil that is obtained by the pressing procedure (Figure 2). Good quality oils, i.e. those with low acidity (<2% free oleic acid) and that meet certain taste, bitterness and spiciness criteria are called “virgin” olive oils or, if their acidity is less than 0.8%, “extra virgin” olive oils. These oils contain the majority of the polyphenols in the starting olives and, after centrifugation and filtration, can be consumed as is.

On the other hand, some olive varieties give an inferior quality oil due to too high acidity (> 2%) and/or an unpleasant smell and taste that does not meet the established criteria. These oils, which are unfit for consumption, are called “lampantes” (a name which comes from their ancient use as fuel in oil lamps) and must be refined as is done for other vegetable oils, i.e. using different physicochemical procedures (neutralization with soda, high temperature bleaching and deodorization, hexane extraction, etc.). These steps remove the compounds responsible for the excess acidity and the unpleasant taste of the oil and produce a “neutral” olive oil that has lost its acidity and its flaws, but that is now devoid of the smell, flavour, colour and most of the phenolic components of the starting virgin olive oil. To stabilize these oils and improve their taste, a certain proportion (15–20%) of virgin olive oil is subsequently added and the final product, which is a mixture of refined olive oil and virgin olive oil, is what is sold in grocery stores as “pure olive oil” or simply “olive oil”.

In short, there are three main types of olive oil on the market: virgin olive oil (VOO), extra virgin olive oil (EVOO), and regular olive oil (OO).

Figure 2. The different types of olive oil. From Gorzynik-Debicka et al. (2018).

 

These manufacturing differences obviously have a huge impact on the amount of polyphenols present in virgin, extra virgin, and refined oils (Table 1). For OO-type olive oils (which contain refined oils), the polyphenols come exclusively from virgin olive oil that has been added to restore a minimum of taste and colour (from yellow to greenish) to the chemically treated oil. The amount of these polyphenols is therefore necessarily less than in VOO and EVOO and, as a general rule, does not exceed 25–30% of the content of these two oils. This difference is particularly striking for certain polyphenols of the secoiridoid family (oleuropein, oleocanthal, oleacein and ligstroside) whose concentrations are 3 to 6 times greater in EVOO than in OO (Table 1). It should be noted, however, that these values ​​can vary greatly depending on the origin and cultivar of the olives; for example, some extra virgin olive oils have been found to contain up to 10 times more hydroxytyrosol and tyrosol than regular olive oils. The same goes for other polyphenols like oleocanthal: an analysis of 175 distinct extra virgin olive oils from Greece and California revealed dramatic variations between the different oils, with concentrations of the molecule ranging from 0 to 355 mg/kg.

It should also be mentioned that even if the quantities of phenolic compounds in regular olive oil are lower than those found in virgin and extra virgin oils, they nevertheless largely exceed those present in other vegetable oils (sunflower, peanut, canola, soy), which contain very little or none at all.

FamilyMoleculesOO (mg/kg)VOO (mg/kg)EVOO (mg/kg)
Secoiridoidsoleocanthal38.95 ± 9.2971.47 ± 61.85142.77 ± 73.17
oleacein57.37 ± 27.0477.83 ± 256.09251.60 ± 263.24
oleuropein (aglycone)10.90 ± 0.0095.00 ± 116.0172.20 ± 64.00
ligstroside (aglycone)15.20 ± 0.0069.00 ± 69.0038.04 ± 17.23
Phenolic alcoholshydroxytyrosol6.77 ± 8.263.53 ± 10.197.72 ± 8.81
tyrosol4.11 ± 2.245.34 ± 6.9811.32 ± 8.53
Flavonoidsluteolin1.17 ± 0.721.29 ± 1.933.60 ± 2.32
apigenin0.30 ± 0.170.97 ± 0.7111.68 ± 12.78
Phenolic acidsp-coumaric -0.24 ± 0.810.92 ± 1.03
ferulic -0.19 ± 0.500.19 ± 0.19
cinnamic - -0.17 ± 0.14
caffeic -0.21 ± 0.630.19 ± 0.45
protocatechuic -1.47 ± 0.56 -
Table 1. Comparison of the content of phenolic compounds in olive oil (OO), virgin olive oil (VOO) and extra virgin olive oil (EVOO). Please note that the large standard deviations of the mean values reflect the huge variations in polyphenol content depending on the region, cultivar, degree of fruit ripeness, and olive oil manufacturing process. Adapted from Lopes de Souza et al. (2017).

 

Anti-inflammatory spiciness
The amounts of polyphenols contained in a bottle of olive oil are not indicated on its label, but it is possible to detect their presence simply by tasting the oil. The polyphenols in olive oil are indeed essential to the organoleptic sensations so characteristic of this oil, in particular the sensation of tickling or stinging in the throat caused by good quality extra virgin oils, what connoisseurs call “ardour”. Far from being a defect, this ardour is considered by experts as a sign of a superior quality oil and, in tasting competitions, the “spiciest” oils are often those that receive the highest honours.

It is interesting to note that it is by tasting different olive oils that a scientist succeeded, by coincidence, in identifying the molecule responsible for the sensation of spiciness caused by extra virgin olive oil (see box).

Plant ibuprofen

Chance often plays a role in scientific discoveries, and this is especially true when it comes to the discovery of the molecule responsible for the typical irritation caused by olive oil. On a trip to Sicily (Italy) to attend a conference on the organoleptic properties of different foods, Dr. Gary Beauchamp and his colleagues were invited by the organizers of the event to a meal where guests were encouraged to taste extra virgin olive oil from olive trees cultivated on their estate. Even though it was the first time he had tasted this type of olive oil, Dr. Beauchamp was immediately struck by the tingling sensation in his throat, which was similar in every way to that caused by ibuprofen, and that he had experienced multiple times as part of his work to replace acetaminophen (paracetamol) with ibuprofen in cough syrups. Suspecting that olive oil contained a similar anti-inflammatory drug, Dr. Beauchamp and his team subsequently managed to isolate the molecule responsible for this irritation, a polyphenol they called “oleocanthal”. They subsequently discovered that oleocanthal had, like ibuprofen, a powerful anti-inflammatory action and that regular consumption of extra virgin olive oil, rich in oleocanthal, provided an intake equivalent to about 10 mg of ibuprofen and therefore may contribute to the well-documented anti-inflammatory effects of the Mediterranean diet. 

But why is the stinging sensation of olive oil only felt in the throat? According to work carried out by the same group, this exclusive localization is due to a specific interaction of oleocanthal (and ibuprofen, for that matter) with a subtype of heat-sensitive receptor (TRPA1). Unlike other types of heat receptors, which are evenly distributed throughout the oral cavity (the TRPV1 receptor activated by the capsaicin of chili peppers, for example, and which causes the burning sensation of some particularly hot dishes), the TRPA1 receptor is located only in the pharynx and its activation by oleocanthal causes a nerve impulse signalling the presence of an irritant only in this region. In short, the more an olive oil stings in the back of the throat, the more oleocanthal it contains and the more anti-inflammatory properties it has. As a general rule, extra virgin olive oils contain more oleocanthal (and polyphenols in general) than virgin olive oils (see Table 1) and are therefore considered superior, both in terms of taste and their positive effects on health.

The superiority of extra virgin olive oil
Several studies have shown that the higher polyphenol content in extra virgin olive oil is correlated with a greater positive effect on several parameters of cardiovascular health than that observed for regular olive oil (see Table 2). For example, epidemiological studies carried out in Spain have reported a decrease of about 10–14% in the risk of cardiovascular disease among regular consumers of extra virgin olive oil, while regular consumption of olive oil had no significant effect. A role of phenolic compounds is also suggested by the EUROLIVE study where the effect of daily ingestion, over a period of 3 weeks, of 25 mL of olive oils containing small (2.7 mg/kg), medium (164 mg/kg), or high (366 mg/kg) amounts of polyphenols was compared. The results show that an increased intake of polyphenols is associated with an improvement in two important risk factors for cardiovascular disease: an increase in the concentration of HDL cholesterol and a decrease in oxidized LDL cholesterol levels. Collectively, the data gathered from the intervention studies indicate that the polyphenols found in extra virgin olive oil play an extremely important role in olive oil’s positive effects on cardiovascular health.

Measured parameterResultsSources
Incidence of cardiovascular disease10% reduction in risk for every 10 g/day of EVOO. No effect of regular OO.Guasch-Ferré et al. (2014)
14% reduction in risk for each 10 g/day of EVOO. No effect of regular OO.Buckland et al. (2012)
Lipid profileLinear increase in HDL cholesterol as a function of the amount of polyphenols.Covas et al. (2006)
Increase in HDL cholesterol only observed with EVOO.Estruch et al. (2006)
Blood glucoseEVOO improves postprandial glycemic profile (decrease in glucose levels and increased insulin).Violo et al. (2015)
Polyphenol-rich EVOO reduces fasting blood glucose and glycated hemoglobin (HbA1c) levels in diabetic patients.Santagelo et al. (2016)
InflammationEVOO, but not OO, induces a decrease in inflammatory markers (TXB(2) and LTB(4)).Bogani et al. (2017)
EVOO, but not OO, induces a decrease in IL-6 and CRP.Fitó et al. (2007)
EVOO, but not OO, decreases the expression of several inflammatory genes.Camargo et al. (2010)
EVOO, but not OO, decreases levels of inflammatory markers sICAM-1 and sVCAM-1.Pacheco et al. (2007)
Oxidative stressStrong in vitro antioxidant activity of phenolic compounds of olive oil.Owen et al. (2000)
Linear decrease in oxidized LDL levels as a function of the amount of polyphenols.Covas et al. (2006)
Lower levels of oxidized LDL after ingestion of EVOO compared to OO.Ramirez-Tortosa et al. (1999)
EVOO phenolic compounds bind to LDL particles and protect them from oxidation.de la Torre-Carbot et al. (2010)
EVOO induces the production of neutralizing antibodies against oxidized LDL.Castañer et al. (2011)
EVOO decreases urinary levels of 8-isoprostane, a marker of oxidative stress.Visioli et al. (2000)
EVOO positively influences the oxidative/antioxidant status of blood plasma.Weinbrenner et al. (2004)
Blood pressureEVOO causes a decrease in systolic and diastolic pressures in hypertensive women.Ruíz-Gutiérrez et al. (1996)
EVOO, but not OO, causes a decrease in systolic pressure in hypertensive coronary patients.Fitó et al. (2005)
EVOO improves postprandial endothelial dilation.Ruano et al. (2005)
EVOO increases the NO vasodilator and decreases systolic and diastolic pressures.Medina-Remón et al. (2015)
EVOO, but not OO, improves vessel dilation in pre-diabetic patients.Njike et al. (2021)
EVOO, but not OO, decreases systolic pressure by 2.5 mmHg in healthy volunteers.Sarapis et al. (2020)
Table 2. Examples of studies comparing the effect of EVOO and OO on several cardiovascular health parameters.

 

In addition to its multiple direct actions on the heart and vessels, it should also be noted that extra virgin olive oil could also exert an indirect beneficial effect, by blocking the formation of the metabolite trimethylamine N-oxide (TMAO) by intestinal bacteria. Several studies have shown that TMAO accelerates the development of atherosclerosis in animal models and is associated with an increased risk of cardiovascular events in clinical studies. Extra virgin olive oils (but not regular olive oils) contain 3,3-dimethyl-1-butanol (DMB), a molecule that blocks a key enzyme involved in TMAO production and prevents development of atherosclerosis in animal models fed a diet rich in animal protein. Taken together, these observations show that there are only advantages to favouring the use of extra virgin olive oil, both for its superior taste and its positive effects on cardiovascular health.

Some people may dislike the slightly peppery taste that extra virgin olive oil leaves in the back of the throat, but interestingly, this irritation is greatly reduced when the oil is mixed with other foods. According to a recent study, this attenuation of the pungent taste is due to the interaction of the polyphenols in the oil with the proteins in food, which blocks the activation of the heat receptors that are normally activated by these polyphenols. People who hesitate to use extra virgin olive oil because of its irritant side can therefore get around this problem and still enjoy the benefits of these oils simply by using it as the main fat when preparing a meal.

Reducing calorie intake by eating more plants

Reducing calorie intake by eating more plants

OVERVIEW

  • Twenty volunteers were fed a low-fat or low-carbohydrate diet in turn for two weeks.
  • Participants on the low-fat diet consumed an average of nearly 700 fewer calories per day than with the low-carbohydrate diet, a decrease correlated with a greater loss of body fat.
  • Compared to the low-carbohydrate diet, the low-fat diet also led to lower cholesterol levels, reduced chronic inflammation, and lowered heart rate and blood pressure.
  • Overall, these results suggest that a diet mainly composed of plants and low in fat is optimal for cardiovascular health, both for its superiority in reducing calorie intake and for its positive impact on several risk factors for cardiovascular disease.

It is estimated that there are currently around 2 billion overweight people in the world, including 600 million who are obese. These statistics are truly alarming because it is clearly established that excess fat promotes the development of several diseases that decrease healthy life expectancy, including cardiovascular disease, type 2 diabetes, and several types of cancer. Identifying the factors responsible for this high prevalence of overweight and the possible ways to reverse this trend as quickly as possible is therefore essential to improve the health of the population and avoid unsustainable pressures on public health systems in the near future.

Energy imbalance
The root cause of overweight, and obesity in particular, is a calorie intake that exceeds the body’s energy needs. To lose weight, therefore, it is essentially a matter of restoring the balance between the calories ingested and the calories expended.

It might seem simple in theory, but in practice most people find it extremely difficult to lose weight. On the one hand, it is much easier to gain weight than to lose weight. During evolution, we have had to deal with periods of prolonged food shortages (and even starvation, in some cases) and our metabolism has adapted to these deficiencies by becoming extremely efficient at accumulating and conserving energy in the form of fat. On the other hand, the environment in which we currently live strongly encourages overconsumption of food. We are literally overwhelmed by an endless variety of attractive food products, which are often inexpensive, easily accessible, and promoted by very aggressive marketing that encourages their consumption. The current epidemic of overweight and obesity thus reflects our biological predisposition to accumulate reserves in the form of fat, a predisposition that is exacerbated by the obesogenic environment that surrounds us.

Eating less to restore balance
The body’s innate tendency to keep energy stored in reserve as fat makes it extremely difficult to lose weight by “burning” those excess calories by increasing the level of physical activity. For example, a person who eats a simple piece of sugar pie (400 calories) will have to walk about 6.5 km to completely burn off those calories, which, of course, is difficult to do on a daily basis. This does not mean that exercise is completely useless for weight loss. Research in recent years shows that exercise can specifically target certain fat stores, especially in the abdominal area. Studies also show that regular physical activity is very important for long-term maintenance of the weight lost from a low-calorie diet. However, there is no doubt that it is first and foremost the calories consumed that are the determining factors in weight gain. Moreover, contrary to what one might think, levels of physical activity have hardly changed for the last thirty years in industrialized countries, and the phenomenal increase in the number of overweight people is therefore mainly a consequence of overconsumption of food. Exercise is essential for the prevention of all chronic diseases and for the maintenance of general good health, but its role in weight loss is relatively minor. For overweight people, the only realistic way to lose weight significantly, and especially to maintain these losses over prolonged periods, is thus to reduce calorie intake.

Less sugar or less fat?
How do we get there? First, it’s important to realize that the surge in the number of overweight people has coincided with a greater availability of foods high in sugar or fat (and sometimes both). All countries in the world, without exception, that have adopted this type of diet have seen their overweight rates skyrocket, so it is likely that this change in eating habits plays a major role in the current obesity epidemic.

However, the respective contributions of sugar and fat to this increase in caloric intake and overweight are still the subjectof vigorous debate:

1) On the one hand, it has been proposed that foods high in fat are particularly obesogenic, since fats are twice as high in calories as carbohydrates, are less effective in causing a feeling of satiety, and improve the organoleptic properties of foods, which generally encourages (often unconscious) overconsumption of food. Therefore, the best way to avoid overeating and becoming overweight would be to reduce the total fat intake (especially saturated fat due to its negative impact on LDL-cholesterol levels) and replace it with complex carbohydrates (vegetables, legumes, whole-grain cereals). This is colloquially called the low-fat approach, advocated for example by the Ornish diet.

2) On the other hand, the exact opposite is proposed, i.e. that it would be mainly carbohydrates that would contribute to overconsumption of food and to the increase in the incidence of obesity. According to this model, carbohydrates in foods in the form of free sugars or refined flours cause insulin levels to rise markedly, causing massive energy storage in adipose tissue. As a result, fewer calories remain available in the circulation for use by the rest of the body, causing increased appetite and overeating to compensate for this lack. In other words, it wouldn’t be because we eat too much that we get fat, but rather because we are too fat we eat too much.

3) By preventing excessive fluctuations in insulin levels, a diet low in carbohydrates would thus limit the anabolic effect of this hormone and, therefore, prevent overeating and the accumulation of excess fat.

Less fat on the menu, fewer calories ingested
To compare the impact of low-carb and low-fat diets on calorie intake, Dr. Kevin Hall’s group (NIH) recruited 20 volunteers who were fed each of these diets in turn for two weeks. The strength of this type of cross-study is that each participant consumes both types of diets and that their effects can therefore be compared directly on the same person.

As shown in Figure 1, the two diets studied were completely opposite of each other, with 75% of the calories in the low-fat (LF) diet coming from carbohydrates versus only 10% from fat, while in the low-carb (LC) diet, 75% of calories were in the form of fat, compared to only 10% from carbohydrates. The LF diet under study consisted exclusively of foods of plant origin (fruits, vegetables, legumes, root vegetables, soy products, whole grains, etc.), while the LC diet contained mainly (82%) animal foods (meat, poultry, fish, eggs, dairy products).

Figure 1. Comparison of the amounts of carbohydrates, fats and proteins present in the low-carbohydrate (LC) and low-fat (LF) diets consumed by study participants. Adapted from Hall et al. (2021).

The study shows that there is indeed a big difference between the two types of diets in the number of calories consumed by participants (Figure 2). Over a two-week period, participants who ate an LF (low-fat) diet consumed an average of nearly 700 calories (kcal) per day less than an LC (low-carbohydrate) diet. This difference in calorie intake is observed for all meals, both at breakfast (240 calories less for the LF diet), at lunch (143 calories less), at dinner (195 calories less), and during snacks taken between meals (128 calories less). This decrease is not caused by a difference in the appreciation of the two diets by the participants, as parallel analyses did not find any difference in the level of appetite of the participants, nor in the degree of satiety and satisfaction generated by the consumption of either diet. However, the LF diet was composed exclusively of plant-based foods and therefore much richer in non-digestible fibres (60 g per day compared to only 20 g for the LC diet), which greatly reduce the energy density of meals (quantity of calories per g of food) compared to the high-fat LC diet. It is therefore very likely that this difference in energy density contributes to the lower calorie intake observed for the low-fat diet.

Overall, these results indicate that a diet consisting of plants, and thus low in fat and high in complex carbohydrates, is more effective than a diet consisting mainly of animal products, high in fat and low in carbohydrates, to limit calorie intake.

Figure 2. Comparison of the daily calorie intake of participants on a low-carbohydrate (LC) or low-fat (LF) diet. From Hall et al. (2021).

Weight loss
Despite the significant difference in calorie intake observed between the two diets, their respective impact on short-term weight loss is more nuanced. At first glance, the LC diet appeared to be more effective than the LF diet in causing rapid weight loss, with about 1 kg lost on average in the first week and almost 2 kg after two weeks, compared to only 1 kg after two weeks of the LF diet (Figure 3). However, further analysis revealed that the weight loss caused by the LC diet was mainly in the form of lean mass (protein, water, glycogen), while this diet had no significant impact on fat loss during this period. Conversely, the LF diet had no effect on this lean body mass, but did cause a significant decrease in body fat, to around 1 kg after two weeks. In other words, only the LF diet caused a loss of body fat during the study period, which strongly suggests that the decrease in calorie intake made possible by this type of diet may facilitate the maintenance of astable body weight and could even promote weight loss in overweight people.

Figure 3. Comparison of changes in body weight (top), lean mass (middle), and body fat (bottom) caused by low-carbohydrate and low-fat diets. From Hall et al. (2021).

Cardiovascular risk factors
In addition to promoting lower calorie intake and fat loss, the LF diet also appears to be superior to the LC diet in terms of its impact on several cardiovascular risk factors (Table 1):

Cholesterol. It is well established that LDL cholesterol levels increase in response to a high intake of saturated fat (see our article on the issue). It is therefore not surprising that the LF diet, which contains only 2% of all calories as saturated fat, causes a significant decrease in cholesterol, both in terms of total cholesterol and LDL cholesterol. At first glance, the high-fat LC diet (containing 30% of the daily calorie intake as saturated fat) does not appear to have a major effect on LDL cholesterol; however, it should be noted that this diet significantly modifies the distribution of LDL cholesterol particles, in particular with a significant increase in small and dense LDL particles. Several studies have reported that these small, dense LDL particles infiltrate artery walls more easily and also appear to oxidize more easily, two key events in the development and progression of atherosclerosis. In sum, just two weeks of a high-fat LC diet was enough to significantly (and negatively) alter the atherogenic profile of participants, which may raise doubts about the long-term effects of this type of diet on cardiovascular health.

Table 1. Variations in certain risk factors for cardiovascular disease following a diet low in carbohydrates or low in fat. From Hall et al. (2021).

Branched-chain amino acids. Several recent studies have shown a very clear association between blood levels of branched-chain amino acids (leucine, isoleucine and valine) and an increased risk of metabolic syndrome and type 2 diabetes, two very important risk factors for cardiovascular diseases. In this sense, it is very interesting to note that the levels of these amino acids are almost twice as high after two weeks of the LC diet compared to the LF diet, suggesting a positive effect of a diet rich in plants and poor in fats in the prevention of these disorders.

Inflammation. Chronic inflammation is actively involved in the formation and progression of plaques that form on the lining of the arteries and can lead to the development of cardiovascular events such as myocardial infarction and stroke. Clinically, this level of inflammation is often determined by measuring levels of high-sensitivity C-reactive protein (hsCRP), a protein made by the liver and released into the blood in response to inflammatory conditions. As shown in Table 1, the LF diet significantly decreases the levels of this inflammatory marker, another positive effect that argues in favour of a plant-rich diet for the prevention of cardiovascular disease.

In addition to these laboratory data, the researchers noted that participants who were fed the LF diet had a slower heart rate (73 vs. 77 beats/min) as well as lower blood pressure (112/67 vs. 116/69 mm Hg) than observed following the LC diet. In the latter case, this difference could be related, at least in part, to the much higher sodium consumption in the LC diet compared to the LF diet (5938 vs. 3725 mg/day).

All of these results confirm the superiority of a diet mainly composed of plants on all the factors involved in cardiovascular health, whether in terms of lipid profile, chronic inflammation, or adequate control of calorie intake necessary to maintain body weight.

To prevent cardiovascular disease, medication should not be a substitute for improved lifestyle

To prevent cardiovascular disease, medication should not be a substitute for improved lifestyle

OVERVIEW

  • Cardiovascular disease dramatically increases the risk of developing serious complications from COVID-19, again highlighting the importance of preventing these diseases in order to live long and healthy lives.
  • And it is possible! Numerous studies clearly show that more than 80% of cardiovascular diseases can be prevented by simply adopting 5 lifestyle habits (not smoking, maintaining a normal weight, eating a lot of vegetables, exercising regularly, and drinking alcohol moderately).

The current COVID-19 pandemic has exposed two major vulnerabilities in our society. The first is, of course, the fragility of our health care system, in particular everything related to the care of the elderly with a loss of autonomy. The pandemic has highlighted serious deficiencies in the way this care is delivered in several facilities, which has directly contributed to the high number of elderly people who have died from the disease. Hopefully, this deplorable situation will have a positive impact on the ways of treating this population in the future.

A second vulnerability highlighted by the pandemic, but much less talked about, is that COVID-19 preferentially affects people who present pre-existing conditions at the time of infection, in particular cardiovascular disease, obesity and type 2 diabetes. These comorbidities have a devastating impact on the course of the disease, with increases in the death rate of 5 to 10 times compared to people without pre-existing conditions. In other words, not only does poor metabolic health have a disastrous impact on healthy life expectancy, it is also a significant risk factor for complications from infectious diseases such as COVID-19. We are therefore not as helpless as we might think in the face of infectious agents such as the SARS-CoV-2 coronavirus: by adopting a healthy lifestyle that prevents the development of chronic diseases and their complications, we simultaneously greatly improve the probability of effectively fighting infection with this type of virus.

Preventing cardiovascular disease
Cardiovascular disease is one of the main comorbidities associated with severe forms of COVID-19, so prevention of these diseases can therefore greatly reduce the impact of this infectious disease on mortality. It is now well established that high blood pressure and high blood cholesterol are two important risk factors for cardiovascular disease. As a result, the standard medical approach to preventing these diseases is usually to lower blood pressure and blood cholesterol levels with the help of drugs, such as antihypertensive drugs and cholesterol-lowering drugs (statins). These medications are particularly important in secondary prevention, i.e. to reduce the risk of heart attack in patients with a history of cardiovascular disease, but they are also very frequently used in primary prevention, to reduce the risk of cardiovascular events in the general population.

The drugs actually manage to normalize cholesterol and blood pressure in the majority of patients, which can lead people to believe that the situation is under control and that they no longer need to “pay attention” to what they eat or be physically active on a regular basis. This false sense of security associated with taking medication is well illustrated by the results of a recent study, conducted among 41,225 Finns aged 40 and over. By examining the lifestyle of this cohort, the researchers observed that people who started medication with statins or antihypertensive drugs gained more weight over the next 13 years, an excess weight associated with an 82% increased risk of obesity compared to people who did not take medication. At the same time, people on medication reported a slight decrease in their level of daily physical activity, with an increased risk of physical inactivity of 8%.

These findings are consistent with previous studies showing that statin users eat more calories, have a higher body mass index than those who do not take this class of drugs, and do less physical activity (possibly due to the negative impact of statins on muscles in some people). My personal clinical experience points in the same direction; I have lost count of the occasions when patients tell me that they no longer have to worry about what they eat or exercise regularly because their levels of LDL cholesterol have become normal since they began taking a statin. These patients somehow feel “protected” by the medication and mistakenly believe that they are no longer at risk of developing cardiovascular disease. This is unfortunately not the case: maintaining normal cholesterol levels is, of course, important, but other factors such as smoking, being overweight, sedentary lifestyle, and family history also play a role in the risk of cardiovascular disease. Several studies have shown that between one third and one half of heart attacks occur in people with LDL-cholesterol levels considered normal. The same goes for hypertension as patients treated with antihypertensive drugs are still 2.5 times more likely to have a heart attack than people who are naturally normotensive (whose blood pressure is normal without any pharmacological treatment) and who have the same blood pressure.

In other words, although antihypertensive and cholesterol-lowering drugs are very useful, especially for patients at high risk of cardiovascular events, one must be aware of their limitations and avoid seeing them as the only way to reduce the risk of cardiovascular events.

Superiority of lifestyle
In terms of prevention, much more can be done by addressing the root causes of cardiovascular disease, which in the vast majority of cases are directly linked to lifestyle. Indeed, a very large number of studies have clearly shown that making only five lifestyle changes can very significantly reduce the risk of developing these diseases (see Table below).

The effectiveness of these lifestyle habits in preventing myocardial infarction is quite remarkable, with an absolute risk drop to around 85% (Figure 1). This protection is seen both in people with adequate cholesterol levels and normal blood pressure and in those who are at higher risk for cardiovascular disease due to high cholesterol and hypertension.

Figure 1. Decreased incidence of myocardial infarction in men combining one or more protective factors related to lifestyle. The comparison of the incidences of infarction was carried out in men who did not have cholesterol or blood pressure abnormalities (upper figure, in blue) and in men with high cholesterol levels and hypertension (lower figure, in orange). Note the drastic drop in the incidence of heart attacks in men who adopted all 5 protective lifestyle factors, even in those who were hypertensive and hypercholesterolemic. Adapted from Åkesson (2014).

Even people who have had a heart attack in the past and are being treated with medication can benefit from a healthy lifestyle. For example, a study conducted by Canadian cardiologist Salim Yusuf’s group showed that patients who modify their diet and adhere to a regular physical activity program after a heart attack have their risk of heart attack, stroke and mortality reduced by half compared to those who do not change their habits (Figure 2). Since all of these patients were treated with all of the usual medications (beta blockers, statins, aspirin, etc.), these results illustrate how lifestyle can influence the risk of recurrence.

Figure 2. Effect of diet and exercise on the risk of heart attack, stroke, and death in patients with previous coronary artery disease. Adapted from Chow et al. (2010).

In short, more than three quarters of cardiovascular diseases can be prevented by adopting a healthy lifestyle, a protection that far exceeds that provided by drugs. These medications must therefore be seen as supplements and not substitutes for lifestyle. The development of atherosclerosis is a phenomenon of great complexity, which involves a large number of distinct phenomena (especially chronic inflammation), and no drug, however effective, will ever offer protection comparable to that provided by a healthy diet, regular physical activity, and maintenance of a normal body weight.

Choosing dietary sources of unsaturated fats has many health benefits

Choosing dietary sources of unsaturated fats has many health benefits

OVERVIEW

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

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

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

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

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

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

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

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

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

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

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

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

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

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


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

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

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

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

The importance of maintaining normal cholesterol levels, even at a young age

The importance of maintaining normal cholesterol levels, even at a young age

OVERVIEW

  • A study of 400,000 middle-aged people (average age 51) shows that above-normal cholesterol levels are associated with a significant increase in the risk of cardiovascular disease in the decades that follow.
  • This risk is particularly high in people who were under the age of 45 at the start of the study, suggesting that prolonged exposure to excess cholesterol plays a major role in increasing the risk of cardiovascular disease.
  • Reducing cholesterol levels as early as possible, from early adulthood, through lifestyle changes (diet, exercise) can therefore limit the long-term exposure of blood vessels to atherogenic particles and thus reduce the cardiovascular events during aging.

It is now well established that high levels of cholesterol in the bloodstream promote the development of atherosclerosis and thereby increase the risk of cardiovascular events such as myocardial infarction and stroke. It is for this reason that the measurement of cholesterol has been part of the basic blood test for more than 30 years and that a deviation from normal values is generally considered a risk factor for cardiovascular disease.

Remember that cholesterol is insoluble in water and must be combined with lipoproteins to circulate in the blood. Routinely, the way to determine cholesterol levels is to measure all of these lipoproteins (what is called total cholesterol) and then distinguish two main types:

  1. HDL cholesterol, colloquially known as “good cholesterol” because it is involved in the elimination of cholesterol and therefore has a positive effect on cardiovascular health;
  2. LDL cholesterol, the “bad” cholesterol because of its involvement in the formation of atherosclerotic plaques that increase the risk of heart attack and stroke.

LDL cholesterol is difficult to measure directly and its concentration is rather calculated from the values determined for total cholesterol, HDL cholesterol and triglycerides using a mathematical formula:

[LDL cholesterol] = [Total cholesterol] – [HDL cholesterol] – [Triglycerides] / 2.2

However, this method has its limits, among other things because a large proportion of cholesterol can be transported by other types of lipoproteins and therefore does not appear in the calculation. However, it is very easy to measure all of these lipoproteins by simply subtracting HDL cholesterol from total cholesterol:

[Total cholesterol] – [HDL cholesterol] = [Non-HDL cholesterol]

This calculation makes it possible to obtain the concentration of what is called “non-HDL” cholesterol, i.e. all of the atherogenic lipoproteins [VLDL, IDL, LDL and Lp(a)] that are deposited at the level of the wall of the arteries and form atheromatous plaques that significantly increase the risk of cardiovascular problems. Although clinicians are more familiar with LDL cholesterol measurement, cardiology associations, including the Canadian Cardiovascular Society, now recommend that non-HDL cholesterol also be used as an alternative marker for risk assessment in adults.

Short-term risks
The decision to initiate cholesterol-lowering therapy depends on the patient’s risk of experiencing a cardiovascular event in the next 10 years. To estimate this risk, clinicians use what is called a “risk score” (the Framingham risk score, for example), a calculation based primarily on the patient’s age, history of cardiovascular disease, family history and certain clinical values ​​(blood pressure, blood sugar, cholesterol). For people who are at high risk of cardiovascular disease, especially those who have suffered a coronary event, there is no hesitation: all patients must be taken care of quickly, regardless of LDL or non-HDL cholesterol levels. Several clinical studies have shown that in this population, the main class of cholesterol-lowering drugs (statins) helps prevent recurrences and mortality, with an absolute risk reduction of around 4%. As a result, these drugs are now part of the standard therapeutic arsenal to treat anyone who has survived a coronary event or who has stable coronary heart disease.

The same goes for people with familial hypercholesterolemia (HF), a genetic disorder that exposes individuals to high levels of LDL cholesterol from birth and to a high risk for cardiovascular events before they even turn 40. A study has just recently shown that HF children who were treated with statins at an early age had a much lower incidence of cardiovascular events in adulthood (1% vs. 26%) than their parents who had not been treated early with statins.

Long-term risks
However, the decision to treat high cholesterol is much more difficult for people who do not have these risk factors. Indeed, when the risk of cardiovascular events over the next 10 years is low or moderate, the guidelines tolerate much higher LDL and non-HDL cholesterol levels than in people at risk: for example, when we usually try to keep LDL cholesterol below 2 mmol/L for people at high risk, a threshold twice as high (5 mmol/L) is proposed before treating people at low risk (Table 1). In this population, there is therefore a great deal of room for maneuver in deciding whether or not to start pharmacological treatment or to fundamentally change lifestyle habits (diet, exercise) to normalize these cholesterol levels.

Table 1. Canadian Cardiovascular Society guidelines for dyslipidemia treatment thresholds. *FRS = Framingham Risk Score. Adapted from Anderson et al. (2016).

 

This decision is particularly difficult for young adults, who are generally considered to be at low risk of cardiovascular events over the next 10 years (age is one of the main factors used for risk assessment and therefore the younger you are, the lower the risk). On the one hand, a young person, say in their early forties, who has above-normal LDL or non-HDL cholesterol, but without exceeding the recommended thresholds and without presenting other risk factors, probably does not have a major risk of being affected by a short-term cardiovascular event. But given their young age, they may be exposed to this excess cholesterol for many years and their risk of cardiovascular disease may become higher than average once they turn 70 or 80.

Recent studies indicate that it would be wrong to overlook this long-term negative impact of higher-than-normal non-HDL cholesterol. For example, it has been shown that an increase in non-HDL cholesterol at a young age (before age 40) remains above normal for the following decades and increases the risk of cardiovascular disease by almost 4 times. Another study that followed for 25 years a young population (average age of 42 years) who presented a low risk of cardiovascular disease at 10 years (1.3%) obtained similar results: compared to people with normal non-HDL cholesterol (3.3 mmol/L), those with non-HDL cholesterol above 4 mmol/L had an 80% increased risk of cardiovascular mortality.   As shown in Table 1, these non-HDL cholesterol values are below the thresholds considered to initiate treatment in people at low risk, suggesting that hypercholesterolemia that develops at a young age, even if it is mild and not threatening in the short term, may nevertheless have longer-term adverse effects.

This concept has just been confirmed by a very large study involving nearly 400,000 middle-aged people (average age 51) who were followed for a median period of 14 years (maximum 43 years). The results show a significant increase as a function of time in the risk of cardiovascular disease based on non-HDL cholesterol levels: compared to the low category (<2.6 mmol/L), the risk increases by almost 4 times for non-HDL cholesterol ≥ 5.7 mmol/L, as much in women (increase from 8% to 34%) as in men (increase from 13% to 44%) (Figure 1).

Figure 1. Increased incidence of cardiovascular disease based on non-HDL cholesterol levels. From Brunner et al. (2019).

The largest increase in risk associated with higher non-HDL cholesterol levels was observed in people who were under 45 years of age at the beginning of the study (risk ratio of 4.3 in women and 4.6 in men for non-HDL cholesterol ≥5.7 mmol/L vs. the reference value of 2.6 mmol/L) (Figure 2). In older people (60 years or more), these risk ratios are much lower (1.4 in women and 1.8 in men), confirming that it is prolonged exposure (for several decades) to high levels of non-HDL cholesterol that plays a major role in increasing the risk of cardiovascular disease.

Figure 2. Age-specific and sex-specific association of non-HDL cholesterol and cardiovascular disease. From Brunner et al. (2019).

According to the authors, there would therefore be great benefits in reducing non-HDL cholesterol levels as soon as possible to limit the long-term exposure of blood vessels to atherogenic particles and thus reduce the risk of cardiovascular events. An estimate based on the results obtained indicates that in people 45 years of age and under who have above-normal non-HDL cholesterol levels (3.7–4.8 mmol/L) and other risk factors (e.g. hypertension), a 50% reduction in this type of cholesterol would reduce the risk of cardiovascular disease at age 75 from 16% to 4% in women and from 29% to 6% in men. These significant reductions in long-term risk therefore add a new dimension to the prevention of cardiovascular disease: it is no longer only the presence of high cholesterol levels which must be considered, but also the duration of exposure to excess cholesterol.

What to do if your cholesterol is high
If your short-term risk of cardiovascular accident is high, for example, because you suffer from familial hypercholesterolemia or you combine several risk factors (heredity of early coronary artery disease, hypertension, diabetes, abdominal obesity), it is certain that your doctor will insist on prescribing a statin if your cholesterol is above normal.

For people who do not have these risk factors, the approach that is generally recommended is to modify lifestyle habits, particularly in terms of diet and physical activity. Several of these modifications have rapidly measurable impacts on non-HDL cholesterol levels: weight loss for obese or overweight people, replacing saturated fat with sources of monounsaturated fat (olive oil, for example) and omega-3 polyunsaturated fats (fatty fish, nuts and seeds), an increase in the consumption of soluble fibres, and the adoption of a regular physical activity program. This roughly corresponds to the Mediterranean diet, a diet that has repeatedly been associated with a decreased risk of several chronic diseases, particularly cardiovascular disease.

The advantage of adopting these lifestyle habits is that not only do they help normalize cholesterol levels, but they also have several other beneficial effects on cardiovascular health and health in general. Despite their well-documented clinical utility, randomized clinical studies indicate that statins fail to completely reduce the risk of cardiovascular events, both in primary and secondary prevention. This is not surprising, since atherosclerosis is a multifactorial disease, which involves several phenomena other than cholesterol (chronic inflammation in particular). This complexity means that no single drug can prevent cardiovascular disease alone. And it is only by adopting a comprehensive approach based on a healthy lifestyle that we can make significant progress in preventing these diseases.

Aerobic fitness is associated with levels of blood metabolites that are good for your health

Aerobic fitness is associated with levels of blood metabolites that are good for your health

A large number of studies indicate that there is a positive association between exercise and good health, particularly good cardiovascular health. Researchers are now focusing their efforts on identifying the physiological and molecular mechanisms underlying these beneficial effects.

A study conducted among 580 young Finnish men shows that aerobic fitness (also known as cardiorespiratory capacity) is associated with levels of several metabolites that are beneficial to health. The approach used in this study is referred to as “metabolomics”, i.e. an approach that aims to identify metabolic differences, for example in the blood of people with a disease (diabetes, cancer) compared to people in good health. Most of the metabolomic studies conducted to date have focused on diseases, but this approach has also been applied recently to determine which metabolites are indicative of good health, particularly with regard to exercise.

Of the 66 metabolites selected in the Finnish study, 48 were at different levels between the group of participants who had the highest aerobic fitness and the one with the lowest aerobic fitness (see Figure 2 and Figure 3 of the original article). These differences include a 44% lower concentration of low-density lipoprotein (LDL, the “bad cholesterol”), an 81% higher concentration of high-density lipoprotein (HDL, the “good” cholesterol), a 52% lower total of triglycerides (Figure 1 below, orange bars). On the other hand, greater muscular strength of the participants was not associated with favourable levels for these same metabolites (Figure 1 below, blue bars).

Figure 1. Main differences in blood metabolites between the participants who had the highest aerobic fitness and those who had the lowest (orange bars) or between the participants who had the highest muscular strength and those who had the lowest (blue bars). * Significant difference (P <0.001 or P <0.002); NS: Not significant difference. From Kujala et al., 2019.

Cholesterol
The more detailed analysis (see Figure 2 in the original article) shows that all LDL and VLDL particles of different sizes (small, medium, large, very large, extremely large) are present in lower concentrations in the blood of participants who have a good aerobic capacity than in participants who have a lower aerobic capacity. On the contrary, all HDL particles (very large, large, or medium-sized), except for small ones, are present in higher concentrations in the group with the highest aerobic fitness. Large-size HDLs are particularly beneficial for good cardiovascular health.

Participants with good cardiorespiratory capacity had 80% less apolipoprotein B (ApoB) in their blood than those who were less fit. ApoB is a protein found in very low-density lipoproteins (VLDL) and low-density lipoproteins (LDL). The measurement of the ApoB makes it possible to estimate the number of particles of cholesterol, which is a good indication of the risk of developing cardiovascular disease. High blood levels of ApoB are therefore a risk marker for cardiovascular disease, independently of the level of LDL-cholesterol.

Triglycerides
A high concentration of triglycerides in the blood is a risk marker for coronary heart disease and is associated with obesity and type 2 diabetes. Excessive consumption of sugars and alcohol (not fat) is generally the cause of a high level of triglycerides in the blood.

Other metabolites
Other important metabolites that are present in lower concentrations in individuals with good aerobic capacity include total fatty acids (-60%), glycerol (-64%), lactate (-34%), pyruvate (-36%), branched-chain amino acids (BCAA) isoleucine (-37%) and leucine (-55%), and amino acids phenylalanine (-54%) and tyrosine (-55%). Interestingly, theunsaturation degree of fatty acid of participants in better aerobic fitness was 59% higher than in less fit participants; asituation conducive to good cardiovascular health knowing that it is saturated fatty acids that, in excess, increase theconcentration of LDL-cholesterol and are atherogenic.

High levels of BCAA, phenylalanine and tyrosine are found in obese people and they have been associated with a 5-fold increased risk of developing type 2 diabetes in two separate cohorts. Lower levels of glycerol and ketone bodies (acetylacetate, 3-hydroxybutyrate) in individuals with a high aerobic capacity suggest an increase in fat degradation.

Several metabolites (19) remain associated with a high aerobic fitness after adjustments to account for age and percentageof body fat. After making the same adjustments, muscular strength was associated with only 8 measures of the “metabolome” and none of these associations related to cholesterol or other blood lipids.

This study found more favourable associations between aerobic fitness and certain metabolites that are risk factors for cardiovascular disease than for high muscular strength. It should not be concluded, however, that muscular endurance exercises are useless, quite the contrary. Indeed, muscle training increases aerobic fitness and is an important component of maintaining and improving the condition of people with chronic diseases and the elderly. It is therefore necessary to combine aerobic and muscular exercises to optimize the benefits for cardiovascular health and overall well-being.