Control of inflammation through diet

Control of inflammation through diet

OVERVIEW

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

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

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

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

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

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

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

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

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

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

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

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

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

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

The importance of properly controlling your blood pressure

The importance of properly controlling your blood pressure

OVERVIEW

  • Hypertension is the main risk factor for cardiovascular disease and is responsible for 20% of deaths worldwide.
  • Early hypertension, before the age of 45, is associated with an increased risk of cardiovascular disease, cognitive decline and premature mortality.
  • Adopting an overall healthy lifestyle (normal weight, not smoking, regular physical activity, moderate alcohol consumption, and a good diet including sodium reduction) remains the best way to maintain adequate blood pressure.

According to the latest data from the Global Burden of Disease Study 2019, excessively high blood pressure was responsible for 10.8 million deaths worldwide in 2019, or 19.2% of all deaths recorded. This devastating impact is a direct consequence of the enormous damage caused by hypertension on the cardiovascular system. Indeed, a very large number of studies have clearly shown that excessive blood pressure, above 130/80 mm Hg (see box for a better understanding of blood pressure values), is closely linked to a significant increased risk of coronary heart disease and stroke.

 

Systolic and diastolic

It is important to remember that blood pressure is always expressed in the form of two values, namely systolic pressure and diastolic pressure. Systolic pressure is the pressure of the blood ejected by the left ventricle during the contraction of the heart (systole), while diastolic pressure is that measured between two beats, during the filling of the heart (diastole). To measure both pressures, the arterial circulation in the arm is completely blocked using an inflatable cuff, then the cuff pressure is allowed to gradually decrease until blood begins to flow back into the artery. This is the systolic pressure. By continuing to decrease the swelling of the cuff, we then arrive at a pressure from which there is no longer any obstacle to the passage of blood in the artery, even when the heart is filling. This is the diastolic pressure. A blood pressure value of 120/80 mm Hg, for example, therefore represents the ratio of systolic (120 mm Hg) and diastolic (80 mm Hg) pressures.

As shown in Figure 1, this risk of dying prematurely from coronary heart disease is moderate up to a systolic pressure of 130 mm Hg or a diastolic pressure of 90 mm Hg, but increases rapidly thereafter to almost 4 times for pressures equal to or greater than 150/98 mm Hg. This impact of hypertension is even more pronounced for stroke, with an 8 times higher risk of mortality for people with systolic pressure above 150 mm Hg and 4 times higher for a diastolic pressure greater than 98 mm Hg (Figure 1, bottom graph). Consequently, high blood pressure is by far the main risk factor for stroke, being responsible for about half of the mortality associated with this disease.


Figure 1. Association between blood pressure levels and the risk of death from coronary heart disease or stroke. From Stamler et al. (1993).

Early hypertension
Blood pressure tends to increase with aging as blood vessels become thicker and less elastic over time (blood circulates less easily and creates greater mechanical stress on the vessel wall). On the other hand, age is not the only risk factor for high blood pressure: sedentary lifestyle, poor diet (too much sodium intake, in particular), and excess body weight are all lifestyle factors that promote the development of hypertension, including in younger people.

In industrialized countries, these poor lifestyle habits are very common and contribute to a fairly high prevalence of hypertensive people, even among young adults. In Canada, for example, as many as 15% of adults aged 20–39 and 39% of those aged 40–59 have blood pressure above 130/80 mm Hg (Figure 2).


Figure 2. Prevalence of hypertension in the Canadian population. Hypertension is defined as systolic pressure ≥ 130 mm Hg or diastolic pressure ≥ 80 mm Hg, according to the 2017 criteria of the American College of Cardiology and the American Heart Association. The data are from Statistics Canada.

This proportion of young adults with hypertension is lower than that observed in older people (three in four people aged 70 and over have hypertension), but it can nevertheless have major repercussions on the health of these people in the longer term. Several recent studies indicate that it is not only hypertension per se that represents a risk factor for cardiovascular disease, but also the length of time a person is exposed to these high blood pressures. For example, a recent study reported that onset of hypertension before the age of 45 doubles the risk of cardiovascular disease and premature death, while onset of hypertension later in life (55 years and older) has a much less pronounced impact (Figure 3). These findings are consistent with studies showing that early hypertension is associated with an increased risk of cardiovascular mortality and damage to target organs (heart, kidneys, brain). In the case of the brain, high blood pressure in young adults has been reported to be associated with an increased risk of cognitive decline at older ages. Conversely, a recent meta-analysis suggests that a reduction in blood pressure with the help of antihypertensive drugs is associated with a lower risk of dementia or reduced cognitive function.

Figure 3. Change in risk of cardiovascular disease (red) or death from all causes (blue) depending on the age at which hypertension begins. Adapted from Wang et al. (2020).

Early hypertension should therefore be considered an important risk factor, and young adults can benefit from managingtheir blood pressure as early as possible, before this excessively high blood pressure causes irreparable damage.

The study of barbershops
In African-American culture, barbershops are gathering places that play a very important role in community cohesion. For health professionals, frequent attendance at these barbershops also represents a golden opportunity to regularly meet Black men to raise their awareness of certain health problems that disproportionately affect them. This is particularly the case with hypertension: African American men 20 years and older have one of the highest prevalence of high blood pressure in the world, with as many as 59% of them being hypertensive. Also, compared to whites, Black men develop high blood pressure earlier in their lives and this pressure is on average much higher.

A recent study indicates that barbershops may raise awareness among African Americans about the importance of controlling their blood pressure and promoting the treatment of hypertension. In this study, researchers recruited 319 African Americans aged 35 to 79 who were hypertensive (average blood pressure approximately 153 mm Hg) and who were regular barbershop customers. Participants were randomly assigned to two groups: 1) an intervention group, in which clients were encouraged to see, in the barbershops, pharmacists specially trained to diagnose and treat hypertension and 2) a control group, in which barbers suggested that clients make lifestyle changes and seek medical attention. In the intervention group, pharmacists met regularly with clients during their barbershop visits, prescribed antihypertensive drugs, and monitored their blood pressure.

After only 6 months, the results obtained were nothing short of spectacular: the blood pressure of the intervention group fell by 27 mm Hg (to reach 125.8 mm Hg on average), compared to only 9.3 mm Hg (to reach 145 mm Hg on average) for the control group. Normal blood pressure (less than 130/80 mm Hg) was achieved in 64% of participants in the intervention group, while only 12% of those in the control group were successful. A recent update of the study showed that the beneficial effects of the intervention were long-lasting, with continued pressure reductions still observed one year after the start of the study.

These reductions in blood pressure obtained in the intervention group are of great importance, as several studies have clearly shown that pharmacological treatment of hypertension causes a significant reduction in the risk of cardiovascular diseases, including coronary heart disease and stroke, as well as kidney failure. This study therefore shows how important it is to know your blood pressure and, if it is above normal, to normalize it with medication or through lifestyle changes.

The importance of lifestyle
This last point is particularly important for the many people who have blood pressure slightly above normal, but without reaching values ​​as high as those of the participants of the study mentioned above (150/90 mm Hg and above). In these people, an increase in the level of physical activity, a reduction in sodium intake, and body weight loss can lower blood pressure enough to allow it to reach normal levels. For example, obesity is a major risk factor for hypertension and a weight loss of 10 kg is associated with a reduction in systolic pressure from 5 mm to 10 mm Hg. This positive influence of lifestyle is observed even in people who have certain genetic variants that predispose them to high blood pressure. For example, adopting an overall healthy lifestyle (normal weight, not smoking, regular physical activity, moderate alcohol consumption, and a good diet including sodium reduction) has been shown to be associated with blood pressure approximately 3 mm Hg lower and a 30% reduction in the risk of cardiovascular disease, regardless of the genetic risk. Conversely, an unhealthy lifestyle increases blood pressure and the risk of cardiovascular disease, even in those who are genetically less at risk of hypertension.

In short, taking your blood pressure regularly, even at a young age, can literally save your life. The easiest way to regularly check your blood pressure is to purchase one of the many models of blood pressure monitors available in pharmacies or specialty stores. Take the measurement in a seated position, legs uncrossed and with the arm resting on a table so that the middle of the arm is at the level of the heart. Two measurements in the morning before having breakfast and drinking coffee and two more measurements in the evening before bedtime (wait at least 2 hours after the end of the meal) generally give an accurate picture of blood pressure, which should be below 135/85 mm Hg on average according to Hypertension Canada.

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.

Plant-based meat substitutes reduce certain cardiovascular risk factors

Plant-based meat substitutes reduce certain cardiovascular risk factors

OVERVIEW

  • Participants in a study were divided into two groups, for eight weeks, one consumed two daily servings of plant-based meat substitutes (Beyond Meat products: burger, mock beef, sausage, mock chicken), while the other group ate the same amount of real meat (beef, pork, chicken).
  • Participants who ate plant-based meat substitutes lost some weight and had significantly lower blood levels of trimethylamine oxide (TMAO) and LDL cholesterol than those who consumed meat during the same period.
  • Plant-based meat substitutes appear to be beneficial for health compared to meat since high levels of TMAO and LDL cholesterol are two risk factors for cardiovascular disease.

In an article published in these pages in 2019, we discussed the merits and drawbacks of new food products that mimic the taste and texture of meat, such as Beyond Meat and Impossible Burger. These products are certainly more environmentally friendly than red meat (beef and pork in particular), which requires a lot of resources that tax the global environment. On the other hand, they are ultra-processed products that contain significant amounts of saturated fat and salt.

To determine whether plant-based meat substitutes could be healthier than meat, the Beyond Meat company funded Dr. Christopher D. Gardner, an independent and renowned researcher at Stanford University School of Medicine in California, to conduct a randomized controlled study. One must be extremely careful with studies funded by the food industry, since publishing only the results that will support the sale of their products is to their advantage. On the other hand, in the case of this study, all precautions seem to have been taken so that there is no influence on the results: study design (randomized and controlled with a crossover design), statistical analyses conducted by a third party who was not involved in the design of the study and data collection. Beyond Meat was not involved in the design of the study, the conduct of the study, or the analysis of the data. In addition, Dr. Gardner stated that he has already completed six food industry-sponsored studies with null findings from the original hypothesis.

The 36 study participants were randomly divided into two groups. During the first eight weeks, one group of participants were assigned to eat two servings/day of plant-based meat substitutes (Beyond Meat products: burger, mock beef, sausages, mock chicken), while the other group consumed two servings/day of meat (beef, pork, chicken). The two groups then switched their diet for the next eight weeks (crossover study design). Fasting levels of lipids, glucose, insulin, and trimethylamine oxide (TMAO) were measured before the start of the study and every two weeks during both phases of the study.

The main endpoint of the study was the blood level of TMAO, an emerging risk factor associated with atherosclerosis and other cardiovascular diseases. The group that consumed meat during the first eight weeks had a significantly higher TMAO mean level than the group that consumed plant-based meat substitutes (4.7 vs. 2.7 µM), as well as a higher LDL cholesterol (the “bad cholesterol”) mean level (121 vs. 110 mg/dL), while the mean HDL cholesterol (the “good cholesterol”) level was not significantly different.

A surprise awaited the researchers: Participants who first consumed plant-based products during the first eight weeks did not see their TMAO levels increase when they ate meat during the second part of the study. Researchers were unable to identify any changes in the microbiome (gut flora) that could have explained this difference. However, it appears that making the participants “vegetarian” for eight weeks caused them to lose the ability to produce TMAO from meat. This effect of a vegetarian diet on the microbiome has already been demonstrated by Dr. Stanley L. Hazen’s team at the Cleveland Clinic. After a few weeks of returning to a carnivorous diet, the microbiome begins to produce TMAO again from red meat and eggs.

TMAO is a metabolite produced by the gut microbiome from carnitine and choline, two compounds found in large quantities in red meat such as beef and pork. High concentrations of TMAO can promote atherosclerosis and thrombosis. Indeed, numerous observational studies and animal models have shown that there is an association between TMAO and cardiovascular risk, and that it is beneficial to reduce the levels of TMAO. It should be noted, however, that a causal link between TMAO and cardiovascular disease has not been established and that it is possible that it is a marker rather than a causal agent of these diseases.

In addition to the favourable effect on TMAO, participants who ate plant-based meat substitutes lost weight (1 kg on average) and had significantly lower LDL-cholesterol levels than those who ate meat (110 vs. 121 mg/dL). These differences were observed regardless of the order in which participants followed the two diets.

Beyond Meat probably hopes that these results will allow them to respond to criticisms about their products, which areultra-processed and contain a lot of salt and almost as much saturated fat as meat. Many people want to reduce their consumption of red meat, but do not like classic vegetarian dishes. It seems to us that if these meat substitutes appeal to consumers concerned about maintaining good health and allow them to reduce their meat consumption, this will be beneficial for them and may encourage them to cook veggie burgers and other plant-based meat substitutes themselves. Who knows, maybe these products will lead to significant changes in diet in the future. Considerably reducing our meat consumption can only be beneficial to our health and that of the planet.

 

To prevent cardiovascular disease, medication should not be a substitute for improved lifestyle

To prevent cardiovascular disease, medication should not be a substitute for improved lifestyle

OVERVIEW

  • Cardiovascular disease dramatically increases the risk of developing serious complications from COVID-19, again highlighting the importance of preventing these diseases in order to live long and healthy lives.
  • And it is possible! Numerous studies clearly show that more than 80% of cardiovascular diseases can be prevented by simply adopting 5 lifestyle habits (not smoking, maintaining a normal weight, eating a lot of vegetables, exercising regularly, and drinking alcohol moderately).

The current COVID-19 pandemic has exposed two major vulnerabilities in our society. The first is, of course, the fragility of our health care system, in particular everything related to the care of the elderly with a loss of autonomy. The pandemic has highlighted serious deficiencies in the way this care is delivered in several facilities, which has directly contributed to the high number of elderly people who have died from the disease. Hopefully, this deplorable situation will have a positive impact on the ways of treating this population in the future.

A second vulnerability highlighted by the pandemic, but much less talked about, is that COVID-19 preferentially affects people who present pre-existing conditions at the time of infection, in particular cardiovascular disease, obesity and type 2 diabetes. These comorbidities have a devastating impact on the course of the disease, with increases in the death rate of 5 to 10 times compared to people without pre-existing conditions. In other words, not only does poor metabolic health have a disastrous impact on healthy life expectancy, it is also a significant risk factor for complications from infectious diseases such as COVID-19. We are therefore not as helpless as we might think in the face of infectious agents such as the SARS-CoV-2 coronavirus: by adopting a healthy lifestyle that prevents the development of chronic diseases and their complications, we simultaneously greatly improve the probability of effectively fighting infection with this type of virus.

Preventing cardiovascular disease
Cardiovascular disease is one of the main comorbidities associated with severe forms of COVID-19, so prevention of these diseases can therefore greatly reduce the impact of this infectious disease on mortality. It is now well established that high blood pressure and high blood cholesterol are two important risk factors for cardiovascular disease. As a result, the standard medical approach to preventing these diseases is usually to lower blood pressure and blood cholesterol levels with the help of drugs, such as antihypertensive drugs and cholesterol-lowering drugs (statins). These medications are particularly important in secondary prevention, i.e. to reduce the risk of heart attack in patients with a history of cardiovascular disease, but they are also very frequently used in primary prevention, to reduce the risk of cardiovascular events in the general population.

The drugs actually manage to normalize cholesterol and blood pressure in the majority of patients, which can lead people to believe that the situation is under control and that they no longer need to “pay attention” to what they eat or be physically active on a regular basis. This false sense of security associated with taking medication is well illustrated by the results of a recent study, conducted among 41,225 Finns aged 40 and over. By examining the lifestyle of this cohort, the researchers observed that people who started medication with statins or antihypertensive drugs gained more weight over the next 13 years, an excess weight associated with an 82% increased risk of obesity compared to people who did not take medication. At the same time, people on medication reported a slight decrease in their level of daily physical activity, with an increased risk of physical inactivity of 8%.

These findings are consistent with previous studies showing that statin users eat more calories, have a higher body mass index than those who do not take this class of drugs, and do less physical activity (possibly due to the negative impact of statins on muscles in some people). My personal clinical experience points in the same direction; I have lost count of the occasions when patients tell me that they no longer have to worry about what they eat or exercise regularly because their levels of LDL cholesterol have become normal since they began taking a statin. These patients somehow feel “protected” by the medication and mistakenly believe that they are no longer at risk of developing cardiovascular disease. This is unfortunately not the case: maintaining normal cholesterol levels is, of course, important, but other factors such as smoking, being overweight, sedentary lifestyle, and family history also play a role in the risk of cardiovascular disease. Several studies have shown that between one third and one half of heart attacks occur in people with LDL-cholesterol levels considered normal. The same goes for hypertension as patients treated with antihypertensive drugs are still 2.5 times more likely to have a heart attack than people who are naturally normotensive (whose blood pressure is normal without any pharmacological treatment) and who have the same blood pressure.

In other words, although antihypertensive and cholesterol-lowering drugs are very useful, especially for patients at high risk of cardiovascular events, one must be aware of their limitations and avoid seeing them as the only way to reduce the risk of cardiovascular events.

Superiority of lifestyle
In terms of prevention, much more can be done by addressing the root causes of cardiovascular disease, which in the vast majority of cases are directly linked to lifestyle. Indeed, a very large number of studies have clearly shown that making only five lifestyle changes can very significantly reduce the risk of developing these diseases (see Table below).

The effectiveness of these lifestyle habits in preventing myocardial infarction is quite remarkable, with an absolute risk drop to around 85% (Figure 1). This protection is seen both in people with adequate cholesterol levels and normal blood pressure and in those who are at higher risk for cardiovascular disease due to high cholesterol and hypertension.

Figure 1. Decreased incidence of myocardial infarction in men combining one or more protective factors related to lifestyle. The comparison of the incidences of infarction was carried out in men who did not have cholesterol or blood pressure abnormalities (upper figure, in blue) and in men with high cholesterol levels and hypertension (lower figure, in orange). Note the drastic drop in the incidence of heart attacks in men who adopted all 5 protective lifestyle factors, even in those who were hypertensive and hypercholesterolemic. Adapted from Åkesson (2014).

Even people who have had a heart attack in the past and are being treated with medication can benefit from a healthy lifestyle. For example, a study conducted by Canadian cardiologist Salim Yusuf’s group showed that patients who modify their diet and adhere to a regular physical activity program after a heart attack have their risk of heart attack, stroke and mortality reduced by half compared to those who do not change their habits (Figure 2). Since all of these patients were treated with all of the usual medications (beta blockers, statins, aspirin, etc.), these results illustrate how lifestyle can influence the risk of recurrence.

Figure 2. Effect of diet and exercise on the risk of heart attack, stroke, and death in patients with previous coronary artery disease. Adapted from Chow et al. (2010).

In short, more than three quarters of cardiovascular diseases can be prevented by adopting a healthy lifestyle, a protection that far exceeds that provided by drugs. These medications must therefore be seen as supplements and not substitutes for lifestyle. The development of atherosclerosis is a phenomenon of great complexity, which involves a large number of distinct phenomena (especially chronic inflammation), and no drug, however effective, will ever offer protection comparable to that provided by a healthy diet, regular physical activity, and maintenance of a normal body weight.

Obesity and heart function

Obesity and heart function

OVERVIEW

  • Obesity is normally associated with a decrease in the heart’s energy metabolism, but it is not clear how the heart adapts to cope with this energy deficit.
  • Study participants who were obese had an average 14% lower phosphocreatine/ATP ratio than non-obese participants, but the total energy supply (ATP) delivered to the heart muscle was preserved by a compensatory mechanism that involves the acceleration of the enzymatic reaction catalyzed by creatine kinase.
  • This adaptation mechanism has negative consequences for obese participants in situations where the workload of the heart increases.
  • Obese participants who successfully lost weight (-11% on average) following a 6-month nutritional intervention saw their myocardial energy parameters return to values ​​similar to those measured in non-obese participants.

Obesity is a major public health problem, which is growing so rapidly in our societies that it is now referred to as an “obesity epidemic” (see this article on the subject). Obesity is a significant risk factor for many cardiovascular diseases, including heart failure (HF) and especially heart failure with preserved ejection fraction (HFpEF). Heart failure is the inability of the heart to supply enough blood to deliver oxygen to tissues while maintaining normal filling pressures. People with HFpEF account for about half of people with heart failure, with the other half living with heart failure with reduced ejection fraction (HFrEF). In the United States, more than 80% of patients with HFpEF are overweight (BMI between 25 and 30) or obese (BMI > 30), twice as many as the general population. Obesity is now a risk factor for HFpEF almost as significant as hypertension. Yet hypertension has received much more attention to date than obesity as a cause of HFpEF.

The mechanisms by which obesity leads to HFpEF are multiple: cardiac overload, systemic inflammation, renal retention, insulin resistance, and alterations in cellular metabolism. The direct effects of obesity on heart muscle cells have recently become the subject of interesting studies. Studies published to date suggest that the accumulation of lipids in the heart has toxic effects that promote cardiac dysfunction in obese people. Obesity is normally associated with a decrease in the heart’s energy metabolism, but it is not clear how the heart adapts to cope with this energy deficit.

A study published in 2020 in the journal Circulation makes an important contribution to our understanding of the relationship between obesity and cardiac energy metabolism. The researchers recruited 80 volunteers who had no known cardiovascular disease, including 35 non-obese people (BMI: 24 ± 3 kg/m2) and 45 obese people (BMI: 35 ± 5 kg/m2). All participants were subjected to a battery of tests before and after the nutritional intervention with obese participants only, which aimed to make them lose weight. Among the various tests performed, nuclear magnetic resonance imaging (NMR) was used to assess cardiac function, abdominal visceral fat volume and in the liver, conventional phosphorus (31P) NMR spectroscopy was used to measure phosphocreatine and ATP (energy sources) at rest, and a more sophisticated variant of phosphorus NMR spectroscopy, called “31P saturation transfer”, was used to evaluate the enzymatic kinetics of creatine kinase, the enzyme that allows the rapid formation of ATP from phosphocreatine in muscle cells (ADP + phosphocreatine + H+ → ATP + creatine).

The study showed that obese participants had on average a phosphocreatine/ATP ratio 14% lower than non-obese participants, but that the total ATP supply delivered to the heart muscle was preserved by a compensatory mechanism that involves acceleration of the enzymatic reaction catalyzed by creatine kinase. Indeed, the resting creatine kinase catalytic constant, kfCKrest was 33% higher in obese participants than in non-obese participants.

The researchers suspected that this adaptation mechanism could have negative consequences in situations where the workload of the heart increases. To test this hypothesis, they induced an increase in cardiac output from the heart by administering dobutamine by infusion to the participants, while doing the imaging and NMR spectroscopy tests described above. In non-obese participants, both ATP delivery and kfCK  increased in response to dobutamine infusion, by 80% and 86%, respectively. In contrast, there was no significant increase in ATP delivery and kfCK in obese participants under the same stress conditions imposed on the heart. In addition, the systolic increase caused by the increased heart workload was lower in obese participants (+16%) than in non-obese participants (+21%).

Impacts of weight loss
Of the 45 obese participants, 36 agreed to participate in a 6-month weight loss nutritional intervention, and of these 27 successfully lost weight (-11% of body weight and -23% of body fat, on average). This weight loss was associated with an improvement in several parameters, including a 13% decrease in blood cholesterol, a 9% decrease in fasting glucose, and a 41% reduction in insulin resistance. Weight loss has also been associated with reduced left ventricular end diastolic mass and volume, improved diastolic function, and increased ability to exercise. Weight loss in obese participants was associated with increased phosphocreatine/ATP ratio and decreased kfCkrest and ATP delivery. In fact, obese participants who were successful in losing weight saw their myocardial energy parameters return to values ​​similar to those measured in non-obese participants.

These findings shed light on the likely cause of the exhaustion symptoms after an effort that are present in the majority of obese people. Fortunately, the decrease in cardiac energy capacity induced by obesity is reversible by weight loss, which represents new avenues for the treatment of cardiomyopathies associated with obesity.