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.

A new metabolite derived from the microbiota linked to cardiovascular disease

A new metabolite derived from the microbiota linked to cardiovascular disease

OVERVIEW

  • Metabolomic screening has identified a new metabolite associated with cardiovascular disease in the blood of people with type 2 diabetes.
  • This metabolite, phenylacetylglutamine (PAGln), is produced by the intestinal microbiota and the liver, from the amino acid phenylalanine from dietary proteins.
  • PAGln binds to adrenergic receptors expressed on the surface of blood platelets, which results in making them hyper-responsive.
  • A beta blocker drug widely used in clinical practice (Carvedilol) blocks the prothrombotic effect of PAGln.

A research group from the Cleveland Clinic in the United States recently identified a new metabolite of the microbiota that is clinically and mechanistically linked to cardiovascular disease (CVD). This discovery was made possible by the use of a metabolomic approach (i.e. the study of metabolites in a given organism or tissue), a powerful and unbiased method that identified, among other things, trimethylamine oxide (TMAO) as a metabolite promoting atherosclerosis and branched-chain amino acids (BCAAs) as markers of obesity.

The new metabolomic screening has identified several compounds associated with one or more of these criteria in the blood of people with type 2 diabetes: 1) association with major adverse cardiovascular events (MACE: myocardial infarction, stroke or death) in the past 3 years; 2) heightened levels of type 2 diabetes; 3) poor correlation with indices of glycemic control. Of these compounds, five were already known: two which are derived from the intestinal microbiota (TMAO and trimethyllysine) and three others that are diacylglycerophospholipids. Among the unknown compounds, the one that was most strongly associated with MACE was identified by mass spectrometry as phenylacetylglutamine (PAGln).

In summary, here is how PAGln is generated (see the left side of Figure 1):

  • The amino acid phenylalanine from dietary proteins (animal and plant origin) is mostly absorbed in the small intestine, but a portion that is not absorbed ends up in the large intestine.
  • In the large intestine, phenylalanine is first transformed into phenylpyruvic acid by the intestinal microbiota, then into phenylacetic acid by certain bacteria, particularly those expressing the porA
  • Phenylacetic acid is absorbed and transported to the liver via the portal vein where it is rapidly metabolized into phenylacetylglutamine or PAGln.

Figure 1. Schematic summary of the involvement of PAGln in the increase in platelet aggregation, athero-thrombosis and major adverse cardiovascular events. From Nemet et al., 2020.

Researchers have shown that PAGln increases the effects associated with platelet activation and the potential for thrombosis in whole blood, on isolated platelets and in animal models of arterial damage.

PAGln binds to cell sites in a saturable manner, suggesting specific binding to membrane receptors. The researchers then demonstrated that PAGln binds to G-protein coupled adrenergic receptors, expressed on the surface of the platelet cell membrane. The stimulation of these receptors by PAGln causes the hyperstimulation of the platelets, which then become hyper-responsive and accelerate the platelet aggregation and the thrombosis process.

Finally, in a mouse thrombus model, it has been shown that a beta blocker drug widely used in clinical practice (Carvedilol) blocks the prothrombotic effect of PAGln. This result is particularly interesting because it suggests that the beneficial effects of beta blockers may be partly caused by reversing the effects of high PAGln levels. The identification of PAGln could lead to the development of new targeted and personalized strategies for the treatment of cardiovascular diseases.

Plant or animal proteins: An impact on health

Plant or animal proteins: An impact on health

OVERVIEW

  • Plant-based proteins meet all the amino acid requirements if care is taken to vary the diet and include plants high in protein such as whole grains, legumes and oleaginous seeds.
  • Excessive consumption of sulfur amino acids, which are found in greater amounts in animal proteins, has been associated with a higher risk of cardiometabolic diseases.
  • In animal models, a limited supply of sulfur amino acids in the diet has the effect of delaying the aging process, inhibiting the onset of age-related diseases and disorders, and increasing life expectancy.
Proteins are essential macromolecules found in all living cells, in microorganisms as well as in plants and animals. Whatever their origin and function, proteins are linear chains of amino acids linked by peptide links, and whose sequence is encoded by a specific gene (DNA). Proteins have very diverse functions and are found in animal cells and organs in the form of structural proteins (e.g., collagen, keratin) and proteins with biological activity: enzymes, contractile proteins (e.g., muscle myosin), hormones (e.g., insulin, growth hormone), defence proteins (e.g., immunoglobulins, fibrinogen), transport proteins (e.g., hemoglobin, lipoproteins), etc.

From a nutritional point of view, the important parameters of dietary protein intake are quantity and quality, particularly with regard to the relative amino acid composition of proteins of plant or animal origin. Of the 20 amino acids, 8 are said to be “essential” or indispensable because they cannot be synthesized by our body and therefore must come from the diet. These are lysine, methionine, phenylalanine, tryptophan, threonine, valine, leucine and isoleucine. The proteins ingested during a meal are “cut” into peptides in the stomach, then into free amino acids during their passage in the intestine. It is these free amino acids and not the proteins that are absorbed in the intestine.

Does the origin of the protein contained in food, i.e., plant or animal, have an impact on health? This is an interesting question that is still being debated. Two questions caught our attention:

1) Does a vegetarian diet meet all the energy and amino acid needs?
2) Why are plant proteins better for health than animal proteins?

Nutritional value of plant protein
Do vegetarians eat enough protein? In developed countries, vegetable proteins from different plants are used in the form of mixtures, especially in vegetarian dishes, and the amount of protein consumed exceeds the recommended nutritional intake. According to data from the EPIC-Oxford study of 58,056 Europeans, all types of diet provide more protein than the Recommended Dietary Allowance (RDA: 0.83 g/kg of body weight/day for adults) and the Estimated Average Requirement (EAR: 0.66 g/kg/day) (see Figure 1 below). Even the vegan diet, with an average daily intake of 0.99 g of protein per kg of body weight, meets protein needs in most cases. However, experts have estimated that a small percentage of vegans may not be getting enough protein. It should be noted that children and adolescents and the elderly need more protein to support growth in the young and to compensate for loss of appetite in the elderly.

Figure 1. Daily protein intake by type of diet. According to data from the EPIC-Oxford study (Sobiecki et al., 2016.)

It is often said, incorrectly, that the vegetarian diet is deficient in amino acids (see this review article). In fact, plant proteins contain all 20 amino acids, including the 8 essential amino acids, but it is true that they generally contain less lysine and methionine than those of animal origin. However, by varying one’s diet and taking care to include legumes, nuts and whole grains (three types of protein-rich foods), it has been shown that the vegetarian diet provides ample amounts of each of the amino acids, including lysine and methionine. For example, in the EPIC-Oxford study, it was estimated that lacto-ovo vegetarians and vegans consume an average of 58 and 43 mg of lysine/kg of body weight every day, respectively, which is significantly higher than the estimated average requirement of 30 mg/kg. In rare cases, a deficiency could occur when a vegetarian person has a poor diet, consisting mainly of starchy foods (pasta, fries, pastries) or of a single food (rice or beans).

Why consume more plant protein?
Recent studies suggest an interesting avenue to explain why plant-based proteins are superior in preventing chronic diseases. Sulfur amino acids (cysteine and methionine) are present in greater quantities in animal proteins; however, the average consumption of an adult far exceeds the amount required to be healthy. Consuming these sulfur amino acids (SAAs) in excess has been associated with a higher risk of cardiometabolic diseases and certain cancers, regardless of the total amount of protein consumed.

The cohort studied was derived from the NHANES III study, conducted between 1988 and 1994 among 11,576 adult Americans. The participants’ average SAA consumption was more than 2.5 times higher than the estimated average requirement, i.e., 39.2 mg/kg/day vs. 15 mg/kg/day. Participants in the first quintile consumed an average of 20.1 mg/kg/day SAAs, while those in the last quintile consumed 62.7 mg/kg/day, or 4.2 times the estimated average requirement. Consumption of excess SAAs was associated with several individual risk factors, including blood levels of cholesterol, glucose, uric acid, urea nitrogen, insulin and glycated hemoglobin.

Several previous studies in animal models have illustrated the effect of a diet limited in SAAs to delay the aging process and inhibit the onset of ageing-related diseases and disorders (see this review article). Benefits of this type of diet on animals include increased life expectancy, reductions in body weight and adiposity, decreased insulin resistance, and positive changes in blood levels of several biomarkers such as insulin, glucose, leptin and adiponectin.

Several animal studies have reported that a diet low in methionine inhibits tumour growth. Indeed, a common feature of some cancers is that their growth and survival require an exogenous supply (from the diet) of methionine. In humans, certain types of vegetarian diets low in methionine could be a useful nutritional strategy for controlling tumour growth.

In summary, it seems beneficial for maintaining good health to reduce the consumption of animal proteins and replace them with plant-based proteins. There is no risk of a protein or essential amino acid deficiency for people who adopt a vegetarian diet, as long as they take care to vary their diet and include plants rich in protein such as whole grains (wheat, rice, rye), legumes (e.g., chickpeas, beans, lentils, soybeans, broad beans) and oilseeds (e.g., nuts, cashews, almonds, hazelnuts).

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.

Effectiveness of exercise to prevent and mitigate diabetes: An important role of the gut microbiota

Effectiveness of exercise to prevent and mitigate diabetes: An important role of the gut microbiota

OVERVIEW

  • In overweight, prediabetic and sedentary men, exercise induced changes in the gut microbiota that are correlated with improvements in blood sugar control and insulin sensitivity.
  • The microbiota of the participants who are “responders” to exercise had a greater ability to produce short chain fatty acids (SCFAs) and to eliminate branched-chain amino acids (BCAAs). Conversely, the microbiota of non-responders was characterized by an increased production of metabolically harmful compounds.
  • Transplantation of the fecal microbiota of responders into obese mice produced roughly the same beneficial effects of exercise on insulin resistance. Such effects were not observed after transplanting the microbiota of non-responders.
Regular exercise has beneficial effects on blood glucose control and insulin sensitivity, and is therefore an interesting strategy to prevent and mitigate type 2 diabetes. Unfortunately, in some people, exercise does not cause a favourable metabolic response, a phenomenon called “exercise resistance”. The causes of this phenomenon have not been clearly established, although some researchers have suggested that genetic predispositions and epigenetic changes may contribute to this.

A growing body of data indicates that an imbalance in the gut microbiota (dysbiosis) plays an important role in the development of insulin resistance and type 2 diabetes. Several different mechanisms are involved, including an increase in intestinal permeability and increased endotoxemia, changes in the production of certain short chain fatty acids and branched-chain amino acids, and disturbances in bile acid metabolism. Changes in the composition and function of the gut microbiota have been observed in people with type 2 diabetes and prediabetics. One study also showed that transplanting a healthy person’s microbiota into the intestines of people with metabolic syndrome results in increased microbial diversity and improved blood sugar control as well as sensitivity to insulin.

The intestinal microbiota (formerly intestinal flora) is a complex ecosystem of bacteria, archaea (small microorganisms without nuclei), eukaryotic microorganisms (fungi, protists) and viruses, which has evolved with human beings for several thousands of years. A human gut microbiota, which can weigh up to 2 kg, is absolutely necessary for digestion, metabolic function, and resistance to infection. The human gut microbiota has an enormous metabolic capacity, with more than 1,000 different species of bacteria and 3 million unique genes (the microbiome).

Recent data indicate that exercise modulates the gut microbiota in humans as well as in other species of animals. For example, it has been found that the gut microbiota of professional athletes is more diverse and has a healthier metabolic capacity than the microbiota of sedentary people. However, it is still unclear how these exercise-induced changes in the microbiota are involved in the metabolic benefits (see figure below).

Figure. Changes in the gut microbiota and intestinal epithelium through exercise and health benefits. BDNF: Brain-derived neurotrophic factor (growth factor). From: Mailing et al., 2019.

A study published in Cell Metabolism tried to answer this question by performing an intervention in overweight, prediabetic and sedentary men. Study participants were randomly assigned to a control group (sedentary) or to a 12-week supervised training program. Blood and fecal samples were collected before and after the procedure. After the 12 weeks, modest but significant weight loss and fat loss were observed in people who exercised, with improvements in several metabolic parameters, such as insulin sensitivity, favourable lipid profiles, improved cardiorespiratory capacity and levels of adipokines (signalling molecules secreted by adipose tissues) which are functionally associated with insulin sensitivity. The researchers observed that there was a high interpersonal variability in the results. After classifying the participants as “non-responders” and “responders”, according to their insulin sensitivity score, the researchers analyzed the composition of each participant’s microbiota.

Among responders, exercise altered the concentration of more than 6 species of bacteria belonging to the genera Firmicutes, Bacteroidetes, and Probacteria. Among these bacteria, those belonging to the genus Bacteroidetes are involved in the metabolism of short chain fatty acids (SCFAs). Among the most striking differences between the microbiota of responders and non-responders, the researchers noted a 3.5-fold increase in the number of Lanchospiraceae bacterium, a butyrate producer (a SCFA), which is an indicator of intestinal health. The bacterium Alistipes shahii, which has already been associated with inflammation and is present in higher amounts in obese people, decreased by 43% in responders, while it increased 3.88 times in non-responders. The Prevotella copri bacteria proliferated at a reduced rate in the responders; it is one of the main bacteria responsible for the production of branched-chain amino acids (BCAAs) in the gut and contributes to insulin resistance.

The researchers then transplanted the fecal microbiota of responders and non-responders into obese mice. The fecal microbiota transplantation (FMT) of the responders had the effect in mice of reducing blood sugar and insulin as well as improving insulin sensitivity, while such favourable effects were not observed in mice that received a FMT from non-responders.

Mice saw their blood levels of SCFAs increase significantly, while the levels of BCAAs (leucine, isoleucine, valine) and aromatic amino acids (phenylalanine, tryptophan) decreased after receiving the microbiota from responders. In contrast, mice that received the microbiota from non-responders saw opposite changes in the levels of these same metabolites. BCAA supplementation attenuated the beneficial effects of FMT from responders on blood sugar regulation and insulin sensitivity, while SCFA supplementation in mice that received the microbiota of non-responders partially corrected the defect in blood glucose regulation and insulin sensitivity.

Taken together, these results suggest that the gut microbiota and its metabolites are involved in the beneficial metabolic effects caused by exercise. In addition, this study indicates that poor adaptation of the gut microbiota is partly responsible for the lack of a favourable metabolic response in people who do not respond to exercise.

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.