Modulation of the gut microbiota by dietary interventions to prevent cardiometabolic diseases

Modulation of the gut microbiota by dietary interventions to prevent cardiometabolic diseases

OVERVIEW

  • In a study of 307 participants, the Mediterranean-style diet was associated with a composition of the gut microbiota conducive to good cardiometabolic health.
  • In another study, intermittent fasting altered the gut microbiota and prevented the development of hypertension in rats that spontaneously became hypertensive as they aged.
  • The metabolism of bile acids modulated by the microbiota has been identified as a regulator of blood pressure.
  • Dietary interventions aimed at modifying the gut microbiota could be a viable non-pharmacological approach to prevent and treat high blood pressure and other conditions.

Cardiometabolic diseases including type 2 diabetes and cardiovascular disease are on the rise in Canada and around the world. These diseases, which reduce the quality of life and life expectancy of those affected and generate significant costs for society, can be prevented by maintaining good lifestyle habits, including a healthy diet and regular exercise.

Recent studies have linked microbial metabolism and immune interactions in the gut and the risk of cardiometabolic disease (see our articles on the subject herehere and here). Two new studies show that the type of diet and the frequency of meals have effects on the risk of metabolic disease, which are in part due to alterations in the gut microbiota. The results of these new studies suggest that modulation of the gut microbiota by dietary interventions could be a new preventive and therapeutic approach.

US researchers analyzed the microbiome data of 307 male participants in the Health Professionals Follow-up Study as well as their eating habits and biomarkers of blood glucose regulation, lipid metabolism and inflammation. The Mediterranean-style diet (consisting mainly of vegetables, legumes, fruits, nuts, olive oil, and some wine and red meat) was associated with a composition of the gut microbiota conducive to good cardiometabolic health. The positive association between the Mediterranean-style diet and a lower risk of cardiometabolic disease was particularly strong among participants whose microbiota contained little Prevotella copri bacteria. Researchers do not yet understand why the Mediterranean diet is less effective in people whose microbiota contains the bacterium Prevotella copri, however, they make several hypotheses that will need to be verified in future studies. In any case, it can be envisaged that prevention approaches may one day be personalized according to the intestinal microbial profile of each person.

Benefits of intermittent fasting for hypertension
Intermittent fasting involves compressing the time during which one eats over a short period (6-8 h) and “fasting” the rest of the day (16-18 h). Intermittent fasting has positive effects on weight and body fat loss, chronic inflammation, metabolism, and cardiovascular health (see our articles on the subject here and here). The main metabolic benefits of intermittent fasting are reduced blood LDL cholesterol levels, increased insulin sensitivity and better blood glucose control in diabetics, reduced oxidative stress and inflammation. On the one hand, we know that an imbalance in the intestinal microbiota (intestinal dysbiosis) contributes to the development of hypertension. On the other hand, studies in recent years have shown that fasting and caloric restriction significantly reduce blood pressure, both in animal models and in hypertensive patients.

A recent study shows that the beneficial effects of intermittent fasting on blood pressure are attributable, at least in part, to the modulation of the gut microbiota. The researchers used an animal model commonly used in hypertension research: spontaneously hypertensive stroke-prone (SHRSP) rats, a unique genetic model of severe hypertension and stroke. Hypertensive SHRSP rats and normotensive Wistar-Kyoto (WKY) rats were subjected for 8 weeks to one or the other of the following diets: 1) ad libitum throughout the study (control groups) or 2) a diet alternating a day with food at will and a day without access to food (intermittent fasting). Hypertensive (SHRSP) and normotensive (WKY) rats in the control groups ingested the same amount of food. In contrast, the rats subjected to intermittent fasting ate more on days with food at will than those in the control groups, presumably to compensate for the fasting day. Despite this, the total amount of food ingested during the study was significantly lower in hypertensive (-27%) and normotensive (-35%) rats subjected to intermittent fasting, compared to animals in the respective control groups that had access to food at will. Despite a similar food intake, the hypertensive rats in the control group gained significantly less weight than the normotensive rats.

As expected, the blood pressure of hypertensive rats measured weekly was significantly higher than that of normotensive rats. In contrast, intermittent fasting significantly reduced blood pressure in hypertensive rats by an average of about 40 mmHg by the end of the study, compared to hypertensive rats who had access to food at will. This significant decrease brought the blood pressure of hypertensive rats to levels comparable to those of normotensive rats.

Role of the gut microbiota in the regulation of blood pressure
Animal models allow experiments on the role of the gut microbiota that could not be done in humans. In order to find out whether the gut microbiota plays a role in the effect of intermittent fasting, the researchers continued their studies by “transplanting” the microbiota from hypertensive and normotensive rats into “germ-free” rats, i.e. rats reproduced under special conditions in such a way that they do not contain any microorganisms.

Germ-free rats that received microbiota from hypertensive rats had significantly higher blood pressure than those that received microbiota from normotensive rats when subjected to the control diet (ad libitum). In contrast, intermittent fasting reduced the blood pressure of germ-free rats that received microbiota from hypertensive rats to levels comparable to those of rats that received microbiota from normotensive rats. These results demonstrate that the alterations in the microbiota of hypertensive rats caused by intermittent fasting are sufficient to cause a reduction in blood pressure. Analysis of the microbiota by whole-genome shotgun sequencing has enabled researchers to identify bile acid metabolism as a potential mediator of blood pressure regulation. Subsequent analyses revealed that the blood levels of 11 bile acids (out of 18) in hypertensive SHRSP rats were significantly lower than those in normotensive rats. In support of the hypothesis, the addition of cholic acid (a precursor of bile acids) in the food or the activation of the bile acid receptor (TGR5) significantly reduced the blood pressure (by 18 mmHg) of hypertensive rats.

In summary, the quality of food and frequency with which we eat has a significant impact on the microorganisms in our microbiota, cardiometabolic risk factors and, ultimately, our overall health. By changing the diet and the frequency of meals, it may be possible to significantly improve the condition of people with chronic diseases.

Control of inflammation through diet

Control of inflammation through diet

OVERVIEW

  • Chronic inflammation is actively involved in the formation and progression of plaques that form on the lining of the arteries, which can lead to the development of cardiovascular events such as myocardial infarction and stroke.
  • Two studies show that people whose diet is anti-inflammatory due to a high intake of plants (vegetables, fruits, whole grains), beverages rich in antioxidants (tea, coffee, red wine) or nuts have a significantly lower risk of being affected by cardiovascular disease.
  • This type of anti-inflammatory diet can be easily replicated by adopting the Mediterranean diet, rich in fruits, vegetables, legumes, nuts and whole grains and which has repeatedly been associated with a lower risk of cardiovascular events.

Clinically, the risk of having a coronary event is usually estimated based on age, family history, smoking and physical inactivity as well as a series of measures such as cholesterol levels, blood sugar level and blood pressure. The combination of these factors helps to establish a cardiovascular disease risk “score”, i.e. the likelihood that the patient will develop heart disease over the next ten years. When this score is moderate (10 to 20%) or high (20% and more), one or more specific drugs are generally prescribed in addition to recommending lifestyle changes in order to reduce the risk of cardiovascular events.

These estimates are useful, but they do not take into account other factors known to play an important role in the development of cardiovascular disease. This is especially true for chronic inflammation, a process that actively participates in the formation and progression of plaques that form on the lining of the arteries and can lead to cardiovascular events such as myocardial infarction and stroke.

The clinical significance of this chronic inflammation is well illustrated by studies of patients who have had a heart attack and are treated with a statin to lower their LDL cholesterol levels. Studies show that a high proportion (about 40%) of these people have excessively high blood levels of inflammatory proteins, and it is likely that this residual inflammatory risk contributes to the high rate of cardiovascular mortality (nearly 30%) that affects these patients within two years of starting treatment, despite a significant reduction in LDL cholesterol. In this sense, it is interesting to note that the canakinumab antibody, which neutralizes an inflammatory protein (interleukin-1 β), causes a slight but significant decrease in major cardiovascular events in coronary patients. Statins, used to lower LDL cholesterol levels, are also believed to have an anti-inflammatory effect (reduction in C-reactive protein levels) that would contribute to reducing the risk of cardiovascular events. One of the roles of inflammation is also demonstrated by the work of Dr. Jean-Claude Tardif of the Montreal Heart Institute, which shows that the anti-inflammatory drug colchicine significantly reduces the risk of recurrence of cardiovascular events.

Reducing chronic inflammation is therefore a very promising approach for decreasing the risk of cardiovascular disease, both in people who have already had a heart attack and are at a very high risk of recurrence and in healthy people who are at high risk of cardiovascular disease.

Anti-inflammatory diet
Two studies published in the Journal of the American College of Cardiology suggest that the nature of the diet can greatly influence the degree of chronic inflammation and, in turn, the risk of cardiovascular disease. In the first of these two articles, researchers analyzed the link between diet-induced inflammation and the risk of cardiovascular disease in 166,000 women and 44,000 men followed for 24 to 30 years. The inflammatory potential of the participants’ diet was estimated using an index based on the known effect of various foods on the blood levels of 3 inflammatory markers (interleukin-6, TNFα-R2, and C-reactive protein or CRP). For example, consumption of red meat, deli meats and ultra-processed industrial products is associated with an increase in these markers, while that of vegetables, fruits, whole grains and beverages rich in antioxidants (tea, coffee, red wine) is on the contrary associated with a decrease in their blood levels. People who regularly eat pro-inflammatory foods therefore have a higher inflammatory food index, while those whose diet is rich in anti-inflammatory foods have a lower index.

Using this approach, the researchers observed that a higher dietary inflammatory index was associated with an increased risk of cardiovascular disease, with a 40% increase in risk in those with the highest index (Figure 1). This increased risk associated with inflammation is particularly pronounced for coronary heart disease (acute coronary syndromes including myocardial infarction) with an increased risk of 46%, but seems less pronounced for cerebrovascular accidents (stroke) (28% increase in risk). The study shows that a higher dietary inflammation index was also associated with two risk markers for cardiovascular disease, higher circulating triglyceride levels as well as lower HDL cholesterol. These results therefore indicate that there is a link between the degree of chronic inflammation generated by diet and the risk of long-term cardiovascular disease, in agreement with data from a recent meta-analysis of 14 epidemiological studies that have explored this association.

Figure 1. Change in the risk of cardiovascular disease depending on the inflammatory potential of the diet. From Li et al. (2020). The dotted lines indicate the 95% confidence interval.

Anti-inflammatory nuts
A second study by a group of Spanish researchers investigated the anti-inflammatory potential of walnuts. Several epidemiological studies have reported that regular consumption of nuts is associated with a marked decrease in the risk of cardiovascular disease. For example, a recent meta-analysis of 19 prospective studies shows that people who consume the most nuts (28 g per day) have a lower risk of developing coronary artery disease (18%) or of dying from these diseases (23%). These reductions in the risk of cardiovascular disease may be explained in part by the decrease in LDL cholesterol (4%) and triglyceride (5%) levels observed following the consumption of nuts in intervention studies. However, this decrease remains relatively modest and cannot alone explain the marked reduction in the risk of cardiovascular disease observed in the studies.

The results of the Spanish study strongly suggest that a reduction in inflammation could greatly contribute to the preventative effect of nuts. In this study, 708 people aged 63 to 79 were divided into two groups, a control group whose diet was completely nut free and an intervention group, in which participants consumed about 15% of their calories daily in the form of walnuts (30–60 g/day). After a period of 2 years, the researchers observed large variations in the blood levels of several inflammatory markers between the two groups (Figure 2), in particular for GM-CSF (a cytokine that promotes the production of inflammatory cells) and interleukin-1 β (a highly inflammatory cytokine whose blood levels are correlated with an increased risk of death during a heart attack). This reduction in IL-1 β levels is particularly interesting because, as mentioned earlier, a randomized clinical study (CANTOS) has shown that an antibody neutralizing this cytokine leads to a reduction in the risk of myocardial infarction in coronary heart patients.

Figure 2. Reduction in blood levels of several inflammatory markers by a diet enriched with nuts. From Cofán et al. (2020). GM-CSF: granulocyte-monocyte colony stimulating factor; hs-CRP: high-sensitivity C-reactive protein; IFN: interferon; IL: interleukin; SAA: serum amyloid A; sE-sel: soluble E-selectin; sVCAM: soluble vascular cell adhesion molecule; TNF: tumour necrosis factor.

Taken together, these studies therefore confirm that an anti-inflammatory diet provides concrete benefits in terms of preventing cardiovascular disease. This preventative potential remains largely unexploited, as Canadians consume about half of all their calories in the form of ultra-processed pro-inflammatory foods, while less than a third of the population eats the recommended minimum of five daily servings of fruits and vegetables and less than 5% of the recommended three servings of whole grains. This imbalance causes most people’s diets to be pro-inflammatory, contributes to the development of cardiovascular diseases as well as other chronic diseases, including certain common cancers such as colon cancer, and reduces the life expectancy.

The easiest way to restore this balance and reduce inflammation is to eat a diet rich in plants while reducing the intake of industrial products. The Mediterranean diet, for example, is an exemplary anti-inflammatory diet due to its abundance of fruits, vegetables, legumes, nuts and whole grains, and its positive impact will be all the greater if regular consumption of these foods reduces that of pro-inflammatory foods such as red meat, deli meats and ultra-processed products. Not to mention that this diet is also associated with a high intake of fibre, which allows the production of anti-inflammatory short-chain fatty acids by the intestinal microbiota, and of phytochemicals such as polyphenols, which have antioxidant and anti-inflammatory properties.

In summary, these recent studies demonstrate once again the important role of diet in preventing chronic disease and improving healthy life expectancy.

Olive oil, the best source of fat for cooking

Olive oil, the best source of fat for cooking

OVERVIEW

  • Over a 24-year period, people who regularly consumed olive oil had an 18% lower risk of coronary heart disease compared to those who never or very rarely consumed it.
  • Replacing only a daily half-serving (5 g) of margarine, butter or mayonnaise with olive oil is associated with a decrease of about 7% in the risk of coronary heart disease.
  • These results confirm that olive oil, especially virgin or extra-virgin olive oil, represents the best source of fat for “healthy” cooking.

It has been known for several years that people who adopt a Mediterranean type diet are less at risk of being affected by cardiovascular diseases. One of the main features of the Mediterranean diet is the abundant use of olive oil, and several studies show that this oil contributes greatly to the protective effect of the Mediterranean diet on cardiovascular health. On the one hand, olive oil has a very high content (70%) of monounsaturated fatty acids, which lower blood LDL-cholesterol levels and improve blood glucose control. On the other hand, virgin and extra virgin olive oils, obtained from the mechanical cold pressing of fruits, also contain significant amounts of several antioxidant and anti-inflammatory compounds such as tocopherols (vitamin E), certain phenolic acids, and several types of polyphenols. In addition to making olive oil much more stable than refined vegetable oils (and reducing the production of oxidized compounds when cooked at high temperature), these compounds certainly contribute to the preventive effects of olive oil, because it has been shown that the reduction in the risk of cardiovascular disease is 4 times greater (14% vs. 3% risk reduction) among consumers of virgin olive oil than among those who use refined olive oil, devoid of these phenolic compounds.

The benefits of preferential use of olive oil have just been confirmed by a study recently published in the Journal of the American College of Cardiology. By examining the eating habits of 92,978 Americans over a 24-year period, a team of researchers at Harvard University observed that those who reported higher consumption of olive oil (> 1/2 tablespoon/day (i.e. >7 g/day) had a risk of coronary heart disease reduced by 18% compared to those who never or very rarely consumed it. The superiority of olive oil over other sources of fat is also suggested by the observation that replacing only half a serving (5 g) of margarine, butter or mayonnaise with olive oil was associated with a decrease of about 7% in the risk of coronary artery disease. There is no doubt: to cook “healthy”, the best source of fat is undoubtedly olive oil.

The cardiovascular benefits observed in this study may seem quite modest, but it should be mentioned that the intake of olive oil in the population studied (inhabitants of the United States) was relatively low, well below what is observed in studies carried out in Europe. For example, the category of the “largest consumers” of olive oil in the U.S. study included anyone who consumed a minimum of 1/2 tablespoon per day, a quantity much lower than that of the participants in the Spanish study PREDIMED (4 tablespoons per day). This higher olive oil intake in the PREDIMED study was associated with a 30% decrease in the risk of cardiovascular events, about double the protective effect seen in the study conducted in the United States. It is therefore likely that the reduction in the risk of coronary heart disease observed in the U.S. study represents minimal protection, which could be even more important by increasing the daily intake of olive oil. In general, experts recommend the consumption of about two tablespoons of olive oil per day to reduce the risk of cardiovascular disease, and to choose virgin or extra-virgin oils because of their polyphenol content.

Choosing dietary sources of unsaturated fats has many health benefits

Choosing dietary sources of unsaturated fats has many health benefits

OVERVIEW

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

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

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

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

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

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

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

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

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

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

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

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

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

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


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

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

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

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

Spicing up the prevention of cardiovascular disease with chili peppers

Spicing up the prevention of cardiovascular disease with chili peppers

OVERVIEW

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

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

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

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

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

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

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

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

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

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

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

Anti-aging effect of a healthy lifestyle

Anti-aging effect of a healthy lifestyle

According to recent studies, adopting a healthy lifestyle, i.e., eating well, exercising, managing stress, and not smoking or drinking too much alcohol, has beneficial effects on the aging of our cells. One of the well-documented phenomena that occur during cellular aging is the degradation of telomeres, unique structures found at the ends of each of our chromosomes; however, a healthy lifestyle can slow down this process

Telomeres and aging
Telomeres are repetitive DNA structures, shaped like a “hairpin”, found at both ends of chromosomes and that ensure the integrity of the genome during cell division. At each division, the telomeres shorten until they become too short to fulfill their protective function: the cell can no longer divide and enters senescence, then dies. Telomere shortening is countered by the action of telomerase, an enzyme that lengthens telomeres during each DNA replication. Telomere shortening in peripheral blood mononuclear cells (lymphocytes and monocytes) is associated with aging and aging-related diseases such as cancer, stroke, dementia, cardiovascular disease, obesity, osteoporosis and type 2 diabetes. Leukocyte telomere length is significantly, albeit weakly, associated with mortality, but cannot predict survival as well as other variables (age, mobility, cognition, smoking, daily life activities).

Physical activity
Physical training improves many aspects of human health, including exercise capacity, blood pressure regulation, insulin sensitivity, lipid profile, reduction of abdominal fat and inflammation. These beneficial effects contribute to increased endothelial function, delay the progression of atherosclerotic lesions, and improve collateralization of blood vessels in people with type 2 diabetes, coronary artery disease and heart failure. The underlying mechanisms are known in part, but details at the molecular level are less well known and are the subject of much research.

The process of cellular aging can be slowed down by sustained exercise. A study published in 2009 showed that sustained physical training in young and middle-aged athletes was associated with higher telomerase activity, increased expression of telomere-stabilizing proteins, and longer telomeres, compared to sedentary people.

The same research group recently conducted a randomized controlled trial to demonstrate that exercise is the cause of increased telomerase activity and telomere length. The results of the study were published in 2018 in the European Heart Journal. The researchers recruited 124 middle-aged men and women (≈50 years) who were in good health, but did not exercise. During the six-month study, participants were randomly divided into four groups: a control group and three groups that did different types of exercise 3 times a week; one group did endurance training (walking/running, 45 min/day); another group exercised at high intensity intervals (4 min at high intensity/4 min rest, repeated 4 times); and the third group did resistance exercises (various weight machines). Blood samples were taken before, during, and at the end of the study to measure telomere length and telomerase activity in leukocytes (white blood cells).

At the end of the study, those who exercised, regardless of the type, had better cardiorespiratory capacity than at the beginning of the study. Telomerase activity was 2–3 times higher in the leukocytes of those who did endurance or interval exercises, compared to the control group. However, this effect was not observed in people who did resistance exercises (weight training). Similarly, telomere length was greater in those who did endurance or interval exercises, but not in those who did resistance exercise.

These results suggest that endurance exercises such as running, brisk walking or swimming are more effective than resistance exercises to keep longer telomeres and delay cellular aging. It should not be concluded, however, that resistance exercises are useless for healthy aging. Resistance exercises increase overall fitness, which is one of the most important indicators of longevity. The researchers suggest further study on the effects of various combinations of endurance and resistance exercises on cellular aging. The lead author concludes that the central message of his study is that it is never too late to start exercising and that it will have beneficial effects on aging.

Proteomic approach to the effects of exercise
Researchers have studied the effects of endurance exercise on the expression of 1,129 proteins in the blood plasma (plasma proteome), classified into 10 modules or patterns according to their level of interconnection. Exercise altered protein expression of four modules in young men, and five modules in older men. Modules affected by the exercise included proteins related to signalling pathways involved in wound healing, apoptosis (cell death) regulation, glucose, insulin and cellular stress signalling, as well as immune and inflammatory responses. In addition, several exercise-affected modules could be correlated with physiological and clinical indicators of a healthy life, including diastolic blood pressure, insulin resistance, maximal aerobic capacity, and vascular endothelial function.

Diet
According to a systematic review of studies published on the subject, five studies indicate that fruit and vegetable consumption is associated with longer telomeres, while eight other studies have not identified a significant association. For foods other than fruits and vegetables, including grains and meats, the data are inconclusive as a whole. Some studies, however, indicate unfavourable associations between certain food groups and the length of telomeres: grains, processed meats, sugary drinks, fats and oils. With regard to eating habits, only the Mediterranean diet has been associated with longer telomeres, but not in all the studies published to date. Future larger-scale observational studies and more focused randomized controlled trials could help to better identify which elements of the diet are beneficial for telomere maintenance and help slow the process of cellular aging.

Effect of stress
Several cross-sectional studies have reported associations between telomere stability and stress exposure (review articles here, here and here). The association lasts throughout life and has been observed in children whose mothers had been under significant stress. It seems that even prenatal stress indirectly experienced by the fœtus is associated with shorter telomeres after birth. Prolonged or repeated exposure to stress is associated with a shortening of telomeres and the development of age-related diseases such as type 2 diabetes, heart disease, dementia and osteoarthritis. According to some studies, people with bipolar disorder, schizophrenia, major depression and post-traumatic stress disorder have shorter telomeres. Stress and mental illnesses therefore have direct effects on the aging of our cells, with consequences for health over the course of life.

Global lifestyle
For men diagnosed with low-grade prostate cancer, adopting a completely different and healthy lifestyle (plant-based, low-fat diet, exercise, stress management, social support) has been associated with a 10% increase in telomere length in their lymphocytes and monocytes, five years after the start of the intervention. Participants in the control group (active surveillance only), on the contrary, saw the average length of their telomeres decrease slightly (-3%). This intervention study included only a small group of people (n = 30), so larger-scale randomized controlled trials are needed to confirm these findings.

There is growing evidence that physical activity has a significant influence on health and quality of life as people age. For example, older people who exercise regularly are often in better shape, they are more muscular, and they are less likely to develop chronic illnesses or physical disabilities than sedentary seniors. Adopting a lifestyle that combines healthy eating, regular exercise and stress management is certainly one of the best things one can do to prevent or fight age-related diseases.