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

Cardiologue et Directeur de la prévention, Institut de Cardiologie de Montréal. Professeur titulaire de clinique, Faculté de médecine de l'Université de Montréal. / Cardiologist and Director of Prevention, Montreal Heart Institute. Clinical Professor, Faculty of Medicine, University of Montreal.7 June 2021

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.

Choosing dietary sources of unsaturated fats has many health benefits

Choosing dietary sources of unsaturated fats has many health benefits

Cardiologue et Directeur de la prévention, Institut de Cardiologie de Montréal. Professeur titulaire de clinique, Faculté de médecine de l'Université de Montréal. / Cardiologist and Director of Prevention, Montreal Heart Institute. Clinical Professor, Faculty of Medicine, University of Montreal.5 February 2020

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 positive effects of flaxseed on cardiovascular health

The positive effects of flaxseed on cardiovascular health

Cardiologue et Directeur de la prévention, Institut de Cardiologie de Montréal. Professeur titulaire de clinique, Faculté de médecine de l'Université de Montréal. / Cardiologist and Director of Prevention, Montreal Heart Institute. Clinical Professor, Faculty of Medicine, University of Montreal.25 January 2018

We often hear that all plants are created equal in terms of positive impact on health, and that the important thing is simply to eat them as often as possible, without worrying about the nature of the fruits, vegetables or seeds consumed. In other words, essentially it would be the quantity that counts, and there would be no difference between eating iceberg lettuce or broccoli, or blueberries rather than a banana. This reductionist view is somewhat outdated, because we now know that there are enormous differences in the biochemical composition of plants, and some of them are in a class of their own for their content in molecules known to have positive effects on health. The inclusion of these foods in dietary habits could thus enhance the benefits associated with a diet rich in plants, especially in terms of prevention of cardiovascular disease.

Flaxseed is a good example of a food that is different from other plants because of certain unique characteristics. On the one hand, these seeds contain very high amounts of polyunsaturated fatty acids (72% of all fats), with three quarters of these fats being the omega-3 type. On the other hand, flaxseed is an exceptional source of lignans, a group of polyphenols with antioxidant and anti-inflammatory properties. In recent years, several studies have suggested that these properties may have several positive effects on cardiovascular health.

Linolenic acid: A fat like no other
Flax seeds are one of only two foods of plant origin (the other being chia seeds) that contain more omega-3 fatty acids (linolenic acid) than omega-6 (linoleic acid). For example, while the omega-3/omega-6 ratio is less than 1 for all commonly consumed vegetable oils, this ratio is 4 for flaxseed, up to 500 times higher than some vegetable sources (sunflower, for example) (Table 1).

Table 1. Proportion (%) of the different types of fatty acids present in various plant sources. Adapted from Dubois (2007). 

Fatty acidsFlaxCanolaSoyCornOliveSunflower
Saturated107.415.714.815.312.8
Monounsaturated18.563.324.228.173.822.4
Polyunsaturated
(total)		71.828.159.857.11066
Linolenic acid
(omega-3)		559.17.810.60.5
Linoleic acid
(omega-6)		16.818.652.156.19.465.6
Omega-3/omega-6
ratio		40.50.20.020.060.008

This predominance of linolenic acid in flaxseed is very interesting because this omega-3 fatty acid has positive effects on several cardiovascular disease risk factors (lowering of LDL cholesterol, lowering of blood pressure), and also has anti-inflammatory and anti-arrhythmic properties. All of these properties may contribute to the decreased risk of cardiovascular events associated with linolenic acid consumption observed in several studies (see Table 2).

Table 2. Examples of studies reporting a positive effect of linolenic acid on cardiovascular health. From Rodriguez-Leyva (2010). 

StudyNumber of participantsMain results
Hu et al. (1999)76,283 (women)A higher intake of linolenic acid is associated with a decrease in fatal myocardial infarction.
Albert et al. (2005)76,283 (women)40% reduction in risk of sudden cardiac death in people consuming the most linolenic acid
Baylin et al. (2003)964The content of linolenic acid in adipose tissue is inversely associated with a decrease in the risk of infarction.
Djoussé et al. (2001)2,004A diet rich in linolenic acid is associated with a lower incidence of coronary calcified atherosclerotic plaques.
Dilecek et al. (1992)12,866 (men)A high intake of linolenic acid is associated with a reduced risk of cardiovascular mortality and all-cause mortality.
Djoussé et al. (2005)4,594A high intake of linolenic acid is associated with a decrease in systolic pressure and the incidence of hypertension.

Linolenic acid can also be converted into DHA and EPA, two long-chain omega-3 fatty acids that have repeatedly been associated with a reduced risk of cardiovascular mortality (this conversion to DHA and EPA is quite low, in the vicinity of 5%, but is generally higher in women). Therefore, while it is now known that simply replacing saturated fats (from animal products) in our diet with unsaturated vegetable fats significantly reduces the risk of developing cardiovascular disease, this protection could be even more important when these unsaturated fats are omega-3.

The Lyon Diet Heart Study is one of the most important demonstrations of the potential of these plant-based omega-3 fatty acids in preventing cardiovascular disease. In this study, 605 myocardial infarction survivors were randomly separated into two groups, one placed on a low-fat diet as recommended by the American Heart Association, and the other on a Mediterranean diet including margarine enriched in linolenic acid (1.1 g/day). After a two-year follow-up, the incidence of cardiovascular disease, including cardiac mortality, decreased dramatically (73%) in the intervention group, raising the interesting possibility that the inclusion of linolenic acid in the diet can significantly improve cardiovascular health.

In primary prevention, most subsequent epidemiological studies have shown that people who have a high intake of linolenic acid are less likely to be affected by cardiovascular disease, a protective effect that has been observed as much in the United States (see here and here), as in Europe (Holland) and Central America (Costa Rica). A meta-analysis of 13 prospective studies indicates that an increased linolenic acid intake of 1 g per day is associated with a 10% reduction in the risk of cardiovascular disease, a protection confirmed by data analysis from 8 American and European studies comprising a total of 148,675 women and 80,368 men. The risk reduction offered by linolenic acid could even be much higher (60%) for people whose intake of long-chain omega-3 (DHA and EPA, found mainly in oily fish) is low (<0.1 g/day). In sum, most of the data collected to date suggests that increased linolenic acid intake is associated with reduced risk of cardiovascular events.

Lignans: Protective phytoestrogens
Another unique feature of flaxseed is its exceptional content of lignans, a group of complex phenolic compounds that have antioxidant and anti-inflammatory properties. While the majority of plants contain relatively low levels of lignans, these molecules are present in much higher quantities in flaxseed (300 mg/100 g), over 1,000 times more than in some commonly consumed foods (Table 3).

Table 3. Main dietary sources of lignans. From Peterson, 2010.

FoodLignans (mg/100 g)
Flax seeds335
Sesame seeds132
Chickpeas35
Green peas8.4
Rye bread (whole grain)1.2
Sunflower seeds0.58
Asparagus0.34
Peanuts0.28
Strawberries0.14

These lignans, mainly secoisolariciresinol and matairesinol, are metabolized by the intestinal microbiota to enterolactone and enterodiol, two molecules that have a weak estrogenic action (phytoestrogens). Since oestrogens exert a cardioprotective action (and would be responsible for the lower incidence of cardiovascular disease in women compared to men), it has been suggested that the estrogenic properties of lignans could help reduce the risk of cardiovascular events. Some epidemiological studies that focused on this issue found that this is indeed the case, i.e., that a higher intake of lignans or an increase in the blood level of enterolactone (produced by the metabolism of lignans) is associated with a reduced risk of cardiovascular events.

Flaxseed and cardiovascular disease
One of the main limitations of studies on the cardioprotective role of linolenic acid and lignans is the low content of these molecules in the traditional western diet. For example, salad dressings are the main source of linolenic acid in several epidemiological studies, while the restricted distribution of lignans in plants means that their intake may be below the threshold required to generate important cardiovascular effects. Therefore, the simultaneous presence of significant amounts of linolenic acid and lignans in flaxseed suggests that the addition of these seeds to dietary habits represents a simple (and economical) way to overcome these deficiencies and improve the beneficial impact of these two classes of molecules on cardiovascular health.

So far, the best-documented effect of flaxseed supplementation is on lowering blood pressure. For example, a randomized, double-blind, placebo-controlled study in Puerto Rico (FLAX-PAD) found that adding 30 grams of ground flaxseed to the diet resulted in a significant decrease in systolic (10 mmHg) and diastolic (7 mmHg) blood pressure. This reduction is even more pronounced in people who were hypertensive at the start of the study (>140 mmHg), with a 15 mmHg reduction in systolic pressure, a decrease even more pronounced than that obtained with the help of some antihypertensive drugs. A meta-analysis of 11 studies on the impact of flaxseed supplementation on blood pressure, however, suggests a more modest antihypertensive effect, with a decrease of approximately 2 mmHg for systolic and 1.2 mmHg for diastolic pressure. This may not seem like much, but studies show that a reduction in blood pressure of this order could decrease stroke mortality by 10% and coronary heart disease by 7%.

It also appears that flaxseed supplementation may lower LDL cholesterol levels, another important risk factor for cardiovascular disease. A meta-analysis of 28 studies showed that flaxseed caused an average decrease of 0.10 mmol/L and 0.08 mmol/L in total cholesterol and LDL cholesterol, respectively, this effect being particularly pronounced in women (- 0.24 mmol/L) and in people who had high cholesterol levels at the beginning of the procedure. A 15% reduction in LDL cholesterol was also observed in patients with lower extremity osteoarthritis, this decrease being added to that caused by statin.

In recent years, much emphasis has been placed on the importance of regularly consuming long-chain omega-3 fatty acids (DHA and EPA), mainly found in oily fish such as salmon, to reduce the risk of cardiovascular diseases. It should not be forgotten, however, that omega-3 of plant origin also have a protective role and that a high intake of foods rich in linolenic acid, such as flax seeds, can also help reduce the risk of cardiovascular events. In fact, a number of studies (here and here, for example) have reported that both types of omega-3 have complementary roles, and a combined increase in linolenic and long-chain omega-3 intake may be desirable for maximum protective effect.

In practical terms, an average daily intake of 2.2 g of linolenic acid is recommended, which corresponds to one tablespoon (15 ml) of flaxseed. It is essential to grind the seeds to increase the absorption of omega-3 fatty acids and allow the transformation of lignans into active phytoestrogens by intestinal bacteria. However, omega-3 fatty acids being very fragile and sensitive to degradation, one should buy whole seeds that can be ground when needed in a simple coffee grinder, and store the ground seeds for a maximum of two weeks in the refrigerator in an airtight container. The ground seeds have a slightly nutty flavour that goes well with cereals, yogurts, smoothies, and can even be used as a salad topping.