Childhood obesity, a ticking time bomb for cardiometabolic diseases

Childhood obesity, a ticking time bomb for cardiometabolic diseases

OVERVIEW

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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


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

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

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

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

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

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

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

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

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

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

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

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

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

Cycling: A particularly beneficial exercise for the health of diabetics

Cycling: A particularly beneficial exercise for the health of diabetics

OVERVIEW

  • Exercise and physical activity bring many benefits for people with type 2 diabetes.
  • Among a large cohort of 110,944 people from 10 European countries, 7,459 people had type 2 diabetes, 37% of whom were cyclists.
  • After a 5-year follow-up, the researchers found that fewer premature deaths and deaths from cardiovascular disease occurred proportionately among cyclists than among non-cyclists.
  • Participants who started cycling after the start of the study also saw their risk of death significantly reduced, showing that it is never too late to get on that bike and reap the health benefits.

Diabetes increases the risk of developing cardiovascular disease and of dying prematurely from cardiovascular causes and from any cause. Regular physical activity and exercise reduce risk factors for cardiovascular disease in people with diabetes.

Benefits of aerobic exercise
In diabetics, aerobic training (brisk walking, running, cycling, etc.) increases insulin sensitivity, mitochondrial density (production of energy in cells), vascular reactivity, immune and pulmonary functions, and cardiac output. In addition, regular training lowers the level of glycated hemoglobin and triglycerides in the blood as well as blood pressure.

Benefits of resistance exercise
Diabetes is a risk factor for having poor muscle tone, and it can lead to a faster decline in muscle strength and function. A few mechanisms have been proposed to explain this phenomenon in diabetics, including: 1) endothelial dysfunction secondary to high blood glucose levels which cause vasoconstriction of the vessels that nourish muscles and 2) disruption of skeletal muscle energy metabolism through a dysfunction of the mitochondria (elements of the cell that produces its energy).

Benefits of resistance training (weightlifting, use of a resistance band, etc.) in the general population include improvements in muscle mass and strength, fitness, bone mineral density, insulin sensitivity, blood pressure, lipid profile, and cardiovascular health. For diabetics (type 2), resistance training improves blood sugar control, insulin resistance, blood pressure, muscle strength, lean body mass vs. fat mass.

Benefits of other types of exercise
People with diabetes are particularly affected by the loss of joint mobility, a condition caused in part by the build-up of end products of glycation that occurs during normal aging, but is accelerated by hyperglycemia. People with diabetes can therefore benefit from stretching exercises that allow them to increase the flexibility and mobility of their joints.

Cycling and mortality risk in diabetics
Is there one physical activity that is more beneficial than others to improve the health of people with diabetes and reduce the risk of premature death? A prospective study of 7,459 adults with diabetes, with an average age of 55.9 years, assessed whether there is an association between time spent cycling and cardiovascular mortality or from any cause. Participants, who had been diabetic for an average of 7.7 years at the start of the study, completed detailed questionnaires upon enrollment and 5 years later. Compared with participants who did not cycle at all (0 minutes/week), those who did had a lower risk of death from any cause, from 22% (1 to 59 min/week) to 32% (150 to 299 min/week). Reductions of the same order of magnitude (21 to 43%) were observed for cardiovascular mortality. These reductions in mortality risk were independent of other physical activities reported by participants and other confounding factors (level of education, smoking, adherence to the Mediterranean diet, total energy intake, occupational physical activity).

Another question the study researchers wanted to answer was whether stopping or starting to cycle during the 5-year follow-up had an effect on the risk of death of participants with diabetes. The results indicate that participants who cycled after the start of the study had a significantly lower risk of cardiovascular and all-cause mortality compared to non-cyclists. Participants who instead stopped cycling after starting the study had a similar risk of premature death to that of non-cyclists. It is therefore never too late to start cycling and reap significant health benefits, provided that this exercise is practised regularly, without interruption.

Other researchers found it surprising that the association between cycling and a reduction in the risk of mortality is independent of other physical activities. They point out that there is a relationship between the amount of physical activity and the reduction in mortality (4% reduction in risk per 15 minutes of additional physical activity per day) for healthy people and those with cardiovascular disease according to published data. They questioned whether a bias comparable to that of the “healthy worker effect” is not at issue here. This bias could be caused in this case by the fact that diabetics who cycle are healthier than those who do not, resulting in lower premature mortality. In their response to this criticism, the study authors say they agree that cyclists might be healthier than non-cyclists, but they say they did all they could to minimize this potential bias by adjusting the results to take into account risk factors for premature mortality, including diet, physical activity other than cycling, incidence of myocardial infarction and cancer, and excluding smokers, former smokers and individuals who play sports. The authors conclude that they are convinced that cycling can directly contribute to reducing premature mortality, but that in this type of study it is always possible that there are known or unknown confounding factors.

An earlier study had previously reported that cycling had advantages over other physical activities. This study was carried out about 20 years ago with 30,640 participants in the Copenhagen region of Denmark. In the 14.5 years of follow-up, people who cycled to work had a 40% lower risk of dying prematurely than non-cyclist participants, after accounting for possible confounding factors, including the amount of physical activity during leisure time.

Cycling requires being fit, having a good sense of balance, and having the financial means to buy a bicycle. In addition, cycling must be done in a safe environment, which is increasingly possible with the addition of cycle paths in recent years. In Quebec, cycling cannot be practised safely during the winter, namely for more than 4 months, but it is fortunately possible to ride a stationary bike at home or in training centres. In recent years, there has been real enthusiasm for cycling, including the electric bicycle, which allows older or less fit people to climb slopes without much effort. Let’s hope that this enthusiasm continues so that more people who are healthy or have a chronic illness can benefit from the health benefits of this extraordinary physical activity.

The benefits of extra virgin olive oil on cardiovascular health

The benefits of extra virgin olive oil on cardiovascular health

OVERVIEW

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

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

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

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

 

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


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

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

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

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

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

 

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

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

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

 

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

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

Plant ibuprofen

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

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

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

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

 

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

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

Chile, an example of aggressive state intervention to combat the obesity epidemic

Chile, an example of aggressive state intervention to combat the obesity epidemic

OVERVIEW

  • Chile, like most countries in Latin America, has seen the incidence of obesity in its population skyrocket over the past 20 years.
  • This rise in overweight is directly correlated with overconsumption of ultra-processed industrial foods, especially sugary drinks.
  • To reverse this situation, a law severely restricting the promotion, sale and labelling of these products was introduced in 2016, and this tough approach seems to be starting to bear fruit.

From a medical point of view, one of the greatest upheavals of the 20th century was certainly the dramatic increase in the body weight of the world population. Globally, recent estimates indicate that about 2 billion adults are overweight (BMI between 25 and 30), including 650 million who are obese (BMI> 30), about three times more than in 1975. This very rapid increase in the proportion of overweight people has several consequences on the health of the population because overweight and obesity are associated with significant increases in the incidence of several chronic diseases, including cardiovascular disease, type 2 diabetes and several types of cancer, that reduce healthy life expectancy. In addition to these chronic diseases, the COVID-19 pandemic has also shown that obesity is associated with an increased risk of developing serious complications of the disease and of dying from it. The increase in the number of overweight people is therefore one of the main public health problems of our time and is in the process of erasing the gains achieved as a result of the sharp decline in smoking in recent years.

From undernutrition to overnutrition
This rapid increase in the incidence of obesity is observed globally, but has been particularly noticeable in low- and middle-income countries. Until the late 1970s, the main nutritional problem faced by these countries was the high food insecurity of their populations and the high proportion of children suffering from malnutrition. With the globalization of trade that began in the 1980s, the standard of living of these populations began to resemble more and more that of richer countries, both for some of its positive aspects (access to safe drinking water, hygiene, reduction of infectious diseases and infant mortality, education) as well as for its negative ones (sedentary lifestyle, diet based on ultra-processed foods and fast food).

The result is that all countries, without exception, that have adopted these new eating habits and the Western way of life now have to deal with a greater proportion of obese individuals. In poorer countries, this “nutritional transition” has been so rapid that the increase in the body weight of the population can also coexist with malnutrition. For poor people, the high availability and low cost of ultra-processed foods provide for their energy needs, but the lack of nutrients in these foods means that the excess of calories ingested is paradoxically accompanied by a nutritional deficiency. While this may seem surprising at first glance, overnutrition and undernutrition can therefore occur simultaneously in a population, sometimes within the same family.

Latin America hit hard
Latin America is probably one of the best examples of the impact of these dietary changes on the incidence of obesity and the diseases associated with being overweight. Mexico, for example, was the country that experienced the largest increase in obesity globally between 1990 and 2010, and in 2014, more than 300 million adults living in Latin America were overweight, including 100 million who were obese. The situation may even worsen over the next few years due to the high incidence of childhood obesity, which reaches, for example, 12% in Chile and 11% in Mexico (a percentage similar to that of Canadian children, among the highest in the world).

The economic growth of the 1990s led to a rush for typical North American products such as fast food, televisions and cars, leading to increased calorie intake and a parallel decrease in physical activity levels. The very high consumption of ultra-processed foods, in particular sugary drinks, is certainly one of the new eating habits that contribute to the increase in overweight of the inhabitants of these regions. Globally, three of the four countries consuming the highest number of calories in the form of sugary drinks are in Latin America, with Chile and Mexico in first and second place, followed by Argentina in fourth place just behind the United States (Figure 1).


Figure 1. Comparison of the number of calories from sugary drinks sold in different countries in 2014. Note the very high consumption of these drinks in Chile (red asterisk), more than twice as high as in Canada (black asterisk). From Popkin (2016).

Several studies indicate that this overconsumption of added sugars is generally associated with a poor quality diet (low in nutrients) and significantly contributes to the development of obesity, type 2 diabetes and cardiovascular disease. This is especially true in Latin America, as some studies indicate that in the presence of a high sugar intake, some people of Hispanic descent are genetically predisposed to develop nonalcoholic fatty liver disease, an abnormal buildup of fat in the liver that is closely related to the development of type 2 diabetes and metabolic syndrome.

Government response
The close link between the consumption of ultra-processed foods and the increased risk of obesity illustrates the chasm between the financial interests of the multinational food companies that manufacture these products and the health of the population. The goal of these companies is obviously not to make people sick, but it is undeniable that their primary goal remains to generate profits, without worrying too much about whether the consumption of their products can lead to the development of a large number of chronic diseases.

Governments do not have this luxury, however, as they have to deal directly with the enormous pressures that diseasesassociated with being overweight place on health systems. A simple and straightforward approach that has been adopted by several countries is to introduce a tax on these industrial food products, in particular soft drinks. The principle is the same as for all taxes on other unhealthy products such as alcohol and tobacco, i.e. higher prices are generally associated with lower consumption. Studies that have examined the impact of this approach for soft drinks indicate that this is indeed the case, with decreases in consumption observed (among others) in Mexico, Berkeley (California) and Barbados. Despite the legendary reluctance of politicians to impose new taxes, there is no doubt that this approach represents a promising tool, especially if the amounts collected are reinvested in order to improve the diet of the population (subsidies for the purchase of fruits and vegetables, for example).

Another, even more promising, approach is to help consumers make an informed choice by informing them of the sugar, fat, salt and calorie content of products. This information currently exists, but in the form of nutritional labels that are quite difficult to interpret. The amounts of sugar, saturated fat, sodium and calories are indeed indicated on these labels, but refer to percentages of the recommended daily intake. For most people, seeing that the sugar content of a particular food is, for example, “15% of the recommended intake” is a rather abstract concept that does not specify whether this amount is low, adequate or too high. A simpler and more straightforward way is to clearly indicate on the front of the product whether it is high in sugar, fat or salt, as is the case in Chile. In response to the rampant rise in obesity in its population, the country’s Ministry of Health has introduced a labelling system, featured on the front of the package, which allows consumers to immediately see whether a product contains high amounts of sugar, saturated fat, sodium and calories (Figure 2).Figure 2. Labels produced by the Chilean Ministry of Health (Ministerio de Salud) and affixed to the packaging of products sold in stores. The labels indicate a high content (alto) in sugar (azúcares), saturated fat (grasas saturadas), salt (sodio) or calories (calorías). From Kanter et al. (2019).

These labels help consumers make better choices and can encourage the industry to reformulate their products to escape this labelling and become more attractive. It should be noted that Health Canada has also developed a labelling project of the same type, but the adoption of this practice is still pending, more than two years after the end of public consultations. Mexico, meanwhile, has recently moved forward with a system similar to that of Chile, as have Peru, Uruguay and Israel.

The Chilean approach is part of a comprehensive plan to fight obesity, largely based on changing a food culture that is far too focused on ultra-processed products. In addition to the new labelling system, Chile’s Law of Food Labelling and Advertising introduced in 2016 prohibits the sale of caloric products (ice cream, soft drinks, chips, etc.) in schools, imposes severe restrictions on the marketing of industrial products (elimination of characters loved by children on cereal boxes, ban on sales of candy containing toys, e.g., Kinder), prohibits the advertising of these products on programs or websites aimed at young people, and imposes an 18% tax on sugary drinks, one of the highest in the world. This strong government intervention seems to be paying off: a recent study shows that the consumption of sugary drinks fell 25% within 18 months of the law’s implementation, while that of bottled water increased by 5%. The authorities are now considering expanding the scope of the law by introducing an additional tax on all junk food products.

In North America, we remain extremely passive in the face of the dramatic increase in the number of overweight people in our society. Yet the burden of overweight-related illnesses weighs heavily on our health care system here too, and as mentioned earlier, the future looks bleak as we are now among the world leaders in childhood obesity. The example of Chile shows that governments have concrete legislative means that can be used to try to reverse this trend. Faced with an industry that refuses to self-discipline, the authorities must take a much more aggressive approach to protect the population from the health problems associated with the overconsumption of ultra-processed foods, especially among young people. The risk of obesity is established very early in life, since half of children and adolescents who become obese are already overweight when they enter kindergarten.

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.

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.