A pro-inflammatory diet increases the risk of dementia

A pro-inflammatory diet increases the risk of dementia

OVERVIEW

  • In a study on aging and diet conducted in Greece, 1,059 older people reported in detail what they ate for three years.
  • At the end of the study, people with the most inflammatory diet had a 3-fold higher risk of developing dementia compared to those whose diet had a low-inflammatory index.
  • The main anti-inflammatory foods are vegetables, fruits, whole grains, tea, and coffee. The main pro-inflammatory foods that should be avoided or eaten infrequently and in small amounts are red meat, deli meats, refined flours, added sugars, and ultra-processed foods.

Dietary Inflammatory Index
Several studies suggest that the nature of the foods we eat can greatly influence the degree of chronic inflammation and, in turn, the risk of chronic disease, including cardiovascular disease. For example, a pro-inflammatory diet has been associated with an increased risk of cardiovascular disease, with a 40% increase in risk in people with the highest index (see our article on the subject).

Pro-inflammatory diet and risk of dementia
In order to see if there is an association between a diet that promotes systemic inflammation and the risk of developing dementia, 1,059 elderly people residing in Greece were recruited as part of the study Hellenic Longitudinal Investigation of Aging and Diet (HELIAD). Only people without a diagnosis of dementia at the start of the study were included in the cohort. The inflammatory potential of the participants’ diet was estimated using the Dietary Inflammatory Index (DII) based on the known effect of various foods on the blood levels of inflammatory markers . The main pro-inflammatory foods are red meat, deli meats, refined flour, added sugars, and ultra-processed foods. Some of the main anti-inflammatory foods are vegetables, fruits, whole grains, tea, coffee, and red wine.

After a follow-up of 3 years on average, 62 people were diagnosed with dementia. Participants who had the diet with the highest inflammatory index had a three-fold higher risk of developing dementia at the end of the study, compared to those with the least inflammatory index. In addition, there appears to be a dose-response relationship, with an increased risk of dementia that increases by 21% for each unit of the inflammatory index.

Inflammation, interleukin-6, and cognitive decline
The study in Greece is not the first to be conducted on the impact of a pro-inflammatory diet on the incidence of dementia. In a Polish study of 222 postmenopausal women, those with cognitive deficits had significantly higher blood levels of interleukin-6 (IL-6; a marker of inflammation), were less educated, and were less physically active, compared to women with normal cognitive functions. Postmenopausal women who had a pro-inflammatory diet were much more likely to have cognitive impairment compared to those who had an anti-inflammatory diet, even after adjusting for age, height, body mass index, level of education, and levels of physical activity. Each one-point increase in the dietary inflammatory index was associated with a 1.55-fold increase in the risk of cognitive impairment.

In addition to these studies, it is interesting to see that a meta-analysis of 7 prospective studies including 15,828 participants showed that there is an association between the concentration of IL-6 in the blood and the overall cognitive decline in the elderly. Participants who had the most circulating IL-6 had a 42% higher risk of suffering cognitive decline than those with low blood IL-6 levels.

Several studies have suggested that systemic inflammation (i.e., outside the central nervous system) may play a role in neurodegeneration, Alzheimer’s disease, and cognitive decline in older adults. People with Alzheimer’s disease and mild cognitive impairment tend to have high blood levels of markers of inflammation (IL-6, TNF-α, CRP). In addition, a study indicates that people who have elevated levels of markers of inflammation during midlife have an increased risk of cognitive decline in subsequent decades.

Since the studies described above are observational, they do not establish a causal link between inflammatory diet and dementia. They only show that there is an association. Further studies are needed in the future to establish a cause and effect relationship and identify the underlying molecular mechanisms.

Evidence from recent studies should encourage experts to more often recommend diets high in flavonoids that decrease systemic inflammation and are conducive to the maintenance of good cognitive health. Mediterranean-type diets or the hybrid MIND diet (Mediterranean-DASH Intervention for Neurodegenerative Delay) with an abundance of plants are particularly effective in reducing or delaying cognitive decline.

Phthalates: A component of certain plastics and cosmetic products harmful to human health

Phthalates: A component of certain plastics and cosmetic products harmful to human health

OVERVIEW

  • Phthalates are chemicals added to plastics to make them more flexible and to some cosmetics to preserve their fragrance.
  • A certain amount of these products are released into the environment, including in food and beverages sold in some plastic containers.
  • Due to their widespread use, phthalates are ingested or absorbed without our knowledge and metabolites of these products are found in most people.
  • Phthalates are endocrine and metabolic disruptors, which are associated with adverse effects on neurodevelopment, childhood asthma, type 2 diabetes, ADHD, childhood and adult obesity, breast and uterine cancer, endometriosis and infertility.
  • Exposure to high-molecular weight phthalates, such as DEHP, has been associated with increased cardiovascular and all-cause mortality.
  • Voices are being raised in the scientific community for the use of phthalates to be subject to stricter regulations.

Phthalates are part of a class of chemicals that are widely used in industry (see Table 1 and Figure 1). High-molecular weight phthalates, such as di(2-ethylhexyl) phthalate (DEHP) and diisononyl phthalate (DiNP), are used as plasticizers to impart flexibility to polyvinyl chloride (PVC) materials used to make food packaging, flooring, and medical equipment (tubing, blood bags). Low-molecular weight phthalates, such as diethyl phthalate (DEP) and dibutyl phthalate (DBP), are added to shampoos, lotions and other personal care products to preserve their fragrance.

Since these phthalates are not chemically bound to plastics, they are released into the environment over time and can enter the human body by ingestion, inhalation and absorption through the skin. Once in the body, phthalates are rapidly metabolized and excreted in urine and faeces, so that half of the phthalates are eliminated within 24 hours of entering the body. Despite this rapid elimination, the population is permanently exposed to phthalates since these products are present in consumer products used almost every day. Metabolites of the phthalates DEHP and DiNP are detected in 98% of the total United States population. Daily exposure to a widely used phthalate, DEHP, has been estimated to range from 3 to 30 µg/kg/day, or 0.21 mg to 2.1 mg per day for a person weighing 70 kg (154 lb.).

Table 1. Main phthalates used in consumer products.   Adapted from Zota et al., 2014.

Phthalate  Abbrev.Restricted use in the United StatesCommon sources
Low-molecular weight
Dimethyl phthalateDMPInsect repellents, plastic bottles, food
Diethyl phthalateDEPPerfumes, deodorants, cosmetics, soaps
Di-n-butyl phthalateDnBP++Cosmetics, medications, food packaging, food, PVC applications
Diisobutyl phthalateDiBPCosmetics, food, food packaging
High-molecular weight
Butylbenzyl phthalateBBzP++PVC flooring, food, food packaging
Dicyclohexyl phthalateDCHPFood, food packaging
Di(2-ethylhexyl) phthalateDEHP++PVC applications, toys, cosmetics, food, food packaging, blood bags, catheters
Di-n-octyl phthalateDnOP+PVC applications, food, food packaging
Diisononyl phthalateDiNP+PVC applications, toys, flooring, wall covering
Diisodecyl phthalateDiDP+PVC applications, toys, wires and cables, flooring

 

Figure 1. Chemical structure of the phthalates most commonly used in industry.

 

Phthalates and cardiovascular and all-cause mortality
A study of 5,303 adults in the National Health and Nutrition Examination Survey (NHANES) cohort assessed the association between phthalate exposure and mortality. Participants provided a urine sample in which the major metabolites of phthalates were measured. Exposure to high-molecular weight phthalates was associated with a significant increase in cardiovascular and all-cause mortality during the duration of the study (2001 to 2010). No significant association was observed for exposure to low-molecular weight total phthalates. Participants who were more exposed to high-molecular weight phthalates (third tertile) had a 48% higher risk of death from any cause than participants who were less exposed (first tertile). Examination of the risk associated with each of the phthalate metabolites revealed an association between an elevated urinary level and a 64% increased risk of cardiovascular mortality for monoethyl phthalate (MEP, a low-molecular weight phthalate). The presence of elevated concentrations of two DEHP (high-molecular weight phthalate) metabolites, MEHHP and MECPP, was associated with a 27% and 32% increased risk of all-cause mortality, respectively, compared to the presence of lower concentrations of these metabolites. A third metabolite of DEHP, MEOHP, was associated with a 74% higher risk of cardiovascular mortality (3rd tertile vs. 1st tertile). Extrapolating the results of their study to the US population aged 55 to 64, the authors estimate that approximately 100,000 deaths/year could be attributed to phthalate exposure, at a societal cost of approximately $39 billion.

Phthalates and where food comes from
One study assessed the phthalate exposure of participants in the NHANES cohort, depending on whether they had a meal the day before outside the home (restaurant, fast food chain, cafeteria) or at home. People who ate out had an average of 35% more phthalates in their urine the next day than people who ate at home, mostly foods purchased from the grocery store. The association between eating out and high urinary phthalate concentration was strongest in adolescents. Among teens, those who reported being heavy consumers of fast food and other foods bought outside the home had up to 55% higher phthalate levels than teens who ate at home. Consumption of certain foods in particular, most notably cheeseburgers and similar sandwiches, was associated with increased cumulative exposure to phthalates, but only when these foods were consumed in cafeterias, fast food outlets, and other restaurants. The study authors find the situation worrisome because almost 2/3 of the population in the United States eats food outside of the home at least once a day.

Phthalates and other plasticizers in fast food
A 2021 study measured the levels of phthalates and another plasticizer in samples of burgers, fries, chicken nuggets, chicken burritos and cheese pizza, as well as in plastic gloves used in fast food restaurants to handle food. Samples came from restaurants of major U.S. chains McDonald’s, Burger King, Pizza Hut, Domino’s, Taco Bell, and Chipotle in the San Antonio, Texas area. DEHT, a new plasticizer used as a replacement for phthalates, was detected in highest amounts in food (median: 2.5 mg/kg) and in gloves (28–37% by weight). DnBP and DEHP phthalates were detected in 81% and 70% of food samples, respectively. DEHT concentrations were particularly high in burritos (6 mg/kg) and in burgers (2.2 mg/kg), and this plasticizer was not present in French fries. Cheese pizza contained the lowest levels of plasticizing chemicals (phthalates or not) among the fast food items analyzed. It should be noted that, unlike phthalates, little data is currently available on the toxicity and health effects of new plasticizers such as DEHT, even though they are increasingly used in industry. The results of this study have implications for equity since the African American population in the United States consumes more fast food than other ethnic groups and is more exposed to chemicals from other sources in the United States in their environment.

Phthalates: endocrine disruptors
In a review of all studies on the impact of phthalate exposure on human health, the authors found strong evidence of unfavourable associations for neurodevelopment, sperm quality, and asthma risk in children, as well as moderate to strong evidence of an association with an anogenital distance abnormality in boys (a marker of exposure to endocrine disruptors). Associations between phthalate exposure and the incidence of type 2 diabetes, endometriosis, low birth weight, low testosterone, ADHD, breast and uterine cancer have also been identified with a moderate level of evidence. Finally, other associations have been identified, but with a lower level of evidence, including premature birth, obesity, autism and hearing loss.

Implications for the public
Standards have been adopted in several countries to limit and, in some cases, prohibit the use of phthalates. For example, the use of certain phthalates in toys for very young children has been banned, as they chew and suck their toys. In cosmetics, the use of DEHP, the most problematic phthalate for health, is banned in Europe and in Canada. According to the European Chemicals Agency (ECHA), the derived no-effect levels (DNEL, or “safe dose”) are 34 µg/kg for DEHP, 8.3 µg/kg for DiBP, 6.7 µg/kg for DnBP, and 500 µg/kg for BBzP. This European agency recommended that the use of these 4 phthalates in the form of mixtures in products be limited to 0.1% (w/w) and that the exception for the use of DEHP in the packaging of medical products be abolished.

A significant problem with these “safe doses” was highlighted for DEHP phthalate since, according to a review of 38 articles, the maximum exposure to DEHP measured in the population is more than 6 times greater than the derived no-effect level (242 vs. 34 µg/kg). In addition, for three other phthalates (DiBP, DnBP and BBzP), the authors reported that adverse health effects were associated with exposure levels much lower than the derived no-effect level established by the ECHA. Among these adverse health effects are increased eczema in children, behavioural changes in children, increased body mass index and waist circumference in women and men, and impacts on the fertility of women and men.

Here are some suggestions for limiting exposure to phthalates:

  • Eat at home as much as possible and limit meals from fast food restaurants to a minimum.
  • In the kitchen, use utensils and containers made of glass, porcelain, stainless steel or wood rather than plastic.
  • Do not heat your meals in the microwave in plastic containers, since the heat increases the release of phthalates in food.
  • Carefully read the list of ingredients for body care products (toothpaste, shampoos, etc.) as manufacturers must indicate the presence of phthalates in their products.
  • For body care, choose natural products that contain few ingredients.
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.

Influenza vaccination reduces the risk of premature death in coronary patients

Influenza vaccination reduces the risk of premature death in coronary patients

OVERVIEW

  • Infection with the influenza virus creates inflammatory conditions that increase the risk of a myocardial infarction.
  • In patients who have had a heart attack, the administration of an influenza vaccine significantly reduces the risk of death within 12 months of the coronary event.
  • These results suggest that influenza vaccination should be considered an integral part of post-infarction treatment.

With the COVID-19 pandemic that has been raging for almost two years now, we sometimes forget that other respiratory viruses exist and can also have very negative impacts on health. This is particularly the case with influenza, one of the most common viral diseases, which affects 5 to 20% of the world’s population each year.

Infection of the airway cells with the influenza virus triggers a myriad of clinical symptoms, the most common being a “runny nose”, sore throat, fever and general discomfort. The human body generally has good resistance to the virus, and in the vast majority of cases healthy people manage to overcome the infection within a few days. However, influenza remains a dangerous disease for people whose immunity is not optimal (young children, the elderly or those affected by a chronic disease) because the virus can cause serious pulmonary complications (pneumonia, hemorrhagic bronchitis) and potentially fatal complications in these people.

In addition to its harmful effects on the lungs, several observations indicate that infection with the influenza virus can also affect the cardiovascular system. For example, it has long been known that the peak of the flu season is correlated with an increase in deaths associated with ischemic diseases such as myocardial infarction and stroke. Some studies have also reported that patients who are admitted to hospital with an acute infarction are significantly more likely to have been affected by a respiratory infection in the days or weeks before their admission. Likewise, other studies have shown that people who see a doctor for an acute respiratory infection or flu symptoms are at greater risk of having a serious cardiovascular event later on.

This link between influenza and cardiovascular disease is particularly well illustrated by the results of a Canadian study published in the New England Journal of Medicine. Researchers found that people who tested positive for any of the different respiratory viruses had a much higher risk of being hospitalized for an acute heart attack within 7 days of diagnosis. This increased risk is particularly high for influenza A and B viruses (5 and 10 times, respectively), but is also observed for infections with syncytial virus (RSV) as well as for other respiratory viruses (adenovirus, metapneumovirus, coronavirus, etc.) (Figure 1). It is therefore certain that these increases in the risk of serious cardiovascular events contribute to the mortality associated with respiratory infections, in particular that caused by influenza viruses.

Figure 1. The impact of different respiratory viruses on the risk of myocardial infarction. From Kwong et al. (2018).

This association between lung infections and the risk of cardiovascular events may be due to the close interaction between these two organs. During gas exchange, venous blood (poor in oxygen) is propelled from the right ventricle of the heart into the pulmonary arteries, oxygenates in the pulmonary capillaries, returns to the left atrium through the pulmonary veins to be finally expelled into the circulation through the aorta. The presence of an inflammatory focus associated with the presence of a lung infection can therefore be transmitted rapidly to the whole body. This is particularly dangerous for the heart because this pro-inflammatory climate caused by the infection causes acute inflammation of the vessel walls and an increased coagulation potential, two phenomena known to promote the rupture of atherosclerotic plaques and cause the obstruction of the coronary arteries responsible for the infarction.

The impact of vaccination
Winter is the peak of the flu season because the influenza virus is highly contagious in low temperatures and low humidity levels, two characteristics of winter weather conditions. Despite imperfect protection (around 50–70% effectiveness, in the best years), vaccination remains the best way to reduce the risk of contracting influenza and at the same time reduce the sometimes severe complications of this infection.

This is especially important for people at high risk due to a history of cardiovascular disease. Several studies have shown that influenza vaccination reduces the incidence of cardiovascular events in patients with coronary heart disease, especially those who have recently had a heart attack. The FLUVACS (FLU Vaccination Acute Coronary Syndromes) randomized study showed that in patients admitted for a heart attack or for angioplasty (placement of a stent to dilate the obstructed coronary artery), vaccination reduced the risk of death from cardiovascular causes after 6 months (75% reduction) and one year (66% reduction). Likewise, the FLUCAD randomized study has shown that vaccination of patients with coronary heart disease (as visualized by angiography) halves the risk of a heart attack in the following year.

The results of a randomized, double-blind study recently published in Circulation provide a clear picture of the benefits of influenza vaccination for people who have had a myocardial infarction. In this multicenter study, patients hospitalized for a heart attack or for revascularization (placement of stents to treat severe obstruction of the coronary arteries) were divided into two groups, a control group (placebo) and a group receiving a vaccine against influenza within 72 hours of hospitalization. To judge the effectiveness of the intervention, the primary endpoint used was a combination of infarction, thrombosis, and all-cause mortality occurring within one year of patient randomization. The incidence of heart attack, cardiovascular mortality, and all-cause mortality was also analyzed separately as secondary endpoints.

As shown in Figure 2, the results of the study are quite dramatic overall. For example, the incidence of the primary endpoint (infarction, thrombosis, and all-cause mortality) was reduced by almost half in vaccinated patients (5.3% vs. 7.2% for placebo). Similar decreases were also observed for secondary endpoints such as all-cause mortality (2.9% vs. 4.9%) and cardiovascular mortality (2.7% vs. 4.5%). Only the decrease in the incidence of myocardial infarction was not significantly changed in the vaccinated patients (2.0% vs. 2.4%). Overall, the results of the study confirm that influenza vaccination of patients who have suffered a heart attack or who are at a very high risk of coronary heart attacks (revascularization) significantly reduces the risk of premature death in the year following hospitalization. These observations are in agreement with a recent meta-analysis, involving nearly 240,000 patients with cardiovascular disease, which showed that influenza vaccination was associated with a reduction in the risk of cardiovascular and all-cause mortality, but not in the incidence of myocardial infarction.

Figure 2. Kaplan-Meier curves of events following the administration of the placebo (red lines) or influenza vaccine (blue lines). The cumulative incidence of events is presented for the primary outcome of the study (a combination of myocardial infarction, thrombosis, and all-cause mortality) (A) and secondary outcomes such as all-cause mortality (B), cardiovascular mortality (C), and myocardial infarction (D). From Fröbert et al. (2021).

It should also be noted that influenza vaccination also appears to be beneficial in primary prevention, as a study carried out on 80,363 people aged 65 and over showed that vaccination reduced the incidence of myocardial infarction by 25% over a period of 13 years. Whether you are healthy or have cardiovascular disease, there are only advantages to getting the influenza vaccine.

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.

Lignans: Compounds of plant origin that promote good cardiovascular health

Lignans: Compounds of plant origin that promote good cardiovascular health

OVERVIEW

  • Dietary lignans are phenolic compounds that come mainly from plant-based foods, especially seeds, whole grains, fruits, vegetables, wine, tea and coffee.
  • Consumption of lignans is associated with a reduced risk of developing cardiovascular disease, according to several well-conducted studies.

There are over 8,000 phenolic and polyphenolic compounds found in plants. These compounds are not nutrients, but they have various beneficial biological activities in the human body. They are generally grouped into 4 classes: phenolic acids, flavonoids, stilbenes (e.g., resveratrol), and lignans. Lignans are dimers of monolignols, which can also be used in the synthesis of a long branched polymer, lignin, found in the walls of the conductive vessels of plants. From a nutritional standpoint, lignins are considered to be a component of insoluble dietary fibre.

Figure 1. Structures of the main dietary lignans

Dietary lignans, the most important of which are matairesinol, secoisolariciresinol, pinoresinol and lariciresinol, come mainly from plant-based foods, particularly seeds, whole grains, fruits, vegetables, wine, tea and coffee (see Table 1). Other lignans are found only in certain types of food, such as medioresinol (sesame seeds, rye, lemon), syringaresinol (grains), sesamin (sesame seeds). Lignans are converted into enterolignans by the gut microbiota, which are then absorbed into the bloodstream and distributed throughout the body.

Table 1. Lignan content of commonly consumed foods.
Adapted from Peterson et al., 2010 and Rodriguez-Garcia et al., 2019.

Several studies indicate that lignans can prevent cardiovascular disease and other chronic diseases, including cancer, and improve cardiovascular health, through its anti-inflammatory and estrogenic properties (the ability to bind to estrogen receptors).

A recently published US study indicates that there is a significant association between dietary intake of lignans and the incidence of coronary heart disease. Among the 214,108 people from 3 cohorts of healthcare professionals, those who consumed the most lignans (total) had a 15% lower risk of developing coronary heart disease than those who consumed little. Considering each lignan separately, the association was particularly favourable for matairesinol (-24%), compared to secoisolariciresinol (-13%), pinoresinol (-11%), and lariciresinol (-11%). There is a nonlinear dose-response relationship for total lignans, matairesinol, and secoisolariciresinol with a plateau (maximum effect) at approximately 300 µg/day, 10 µg/day, and 100 µg/day, respectively. Canadians consume an average of 857 µg of lignans per day, enough to benefit from the positive effects on cardiovascular health, but residents of some Western countries such as the United Kingdom, the United States and Germany do not have an optimal intake of lignans (Table 2).

The favourable association for lignans was especially apparent among participants who had a high dietary fibre intake. The authors of the study suggest that fibre, by supporting a healthy microbiota, may promote the production of enterolignans in the gut.

Table 2. Daily intake of lignans in Western countries.
Adapted from Peterson et al., 2010.

PREDIMED (Prevención con Dieta Mediterránea), a recognized study conducted among over 7,000 Spaniards (55–80 years old) at high risk of developing cardiovascular disease, compared the Mediterranean diet (supplemented with nuts and extra virgin olive) to a low-fat diet advocated by the American Heart Association for the prevention of cardiovascular disease (CVD). In this study, the Mediterranean diet was clearly superior to the low-fat diet in preventing CVD, so the study was stopped after 4.8 years for ethical reasons. Further analysis of the PREDIMED data showed that there is a very favourable association between a high dietary intake of polyphenols and the risk of CVD. Participants who consumed the most total polyphenols had a 46% lower risk of CVD than those who consumed the least. The polyphenols that were most strongly associated with reduced risk of CVD were flavanols (-60%), hydroxybenzoic acids (-53%), and lignans (-49%). It should be noted that the nuts and extra virgin olive oil that were consumed daily by participants in the PREDIMED study contain appreciable amounts of lignans.

Another analysis  of data from the PREDIMED study showed a favourable association between total polyphenol intake and the risk of death from any cause. A high intake of total polyphenols, compared to a low intake, was associated with a 37% reduction in the risk of premature mortality. Stilbenes and lignans were the most favourable polyphenols for reducing the risk of mortality, by 52% and 40%, respectively. In this case, flavonoids and phenolic acids were not associated with a significant reduction in mortality risk.

No randomized controlled studies on phenolic compounds and the risk of CVD have been performed to date. There is therefore no direct evidence that lignans protect the cardiovascular system, but all the data from population studies suggests that it is beneficial for health to increase the dietary intake of lignans and therefore to eat more fruits, vegetables, whole grains, legumes, nuts and extra virgin olive oil, which are excellent sources of these still too little known plant-based compounds.