The cardiovascular benefits of soy

The cardiovascular benefits of soy

OVERVIEW

  • Asians have a much lower incidence of cardiovascular disease than North Americans, a difference that has been attributed, at least in part, to their high consumption of soybeans.
  • This protection is due to soy’s high content of isoflavones, a class of polyphenols that have several positive effects on the cardiovascular system.
  • A recent study carried out among 210,700 Americans (168,474 women and 42,226 men) has just confirmed this reduction in the risk of coronary heart disease associated with the consumption of soybeans, illustrating how this legume is an attractive alternative to meat as a source of protein.

It has been known for several years that people in Asian countries have a much lower incidence of cardiovascular disease than in the West. The study of migrant populations has shown that this difference is not due to genetic factors. For example, an analysis carried out in the 1970s revealed that the Japanese who had emigrated to California had twice the incidence of coronary heart disease than that of their compatriots who remained in Japan. It should be mentioned that these Asia-America differences are also observed for several types of cancer, in particular breast cancer. Asian women (China, Japan, Korea) have one of the lowest incidences of breast cancer in the world, but this cancer can become up to 4 times more common as a result of their migration to America, and its incidence even becomes similar to that of third generation Americans. The rapid rise in cardiovascular disease or cancer following migration to the West therefore suggests that abandoning the traditional lifestyle of Asians for the one in vogue in North America greatly favours the development of these diseases.

One of the differences between the Asian and North American lifestyles that has long interested researchers is the huge gap in soy consumption. While an average of 20 to 30 g of soy protein is consumed daily in Japan and Korea, this consumption barely reaches 1 g per day in the United States (Figure 1). It is proposed that this difference could contribute to the higher incidence of cardiovascular disease in the West for two main reasons:

  • Like all members of the legume family (lentils, peas, etc.), soy is an excellent source of fibre, vitamins, minerals, and polyunsaturated fats, nutrients known to be beneficial to heart and vessel health;
  • Soybeans are an exceptional source of isoflavones, a class of polyphenols found almost exclusively in this legume. The main isoflavones in soybeans are genistein, daidzein and glycitein (Figure 2), these molecules being present in varying amounts depending on the degree of processing of soybeans.

Figure 1. Comparison of the amounts of soybeans consumed daily by people in different countries. From Pabich and Materska (2019).

 


Figure 2. Molecular structures of the main isoflavones.
Note that equol is not present in soy products, but is rather generated by the gut microbiome following their ingestion.

The highest concentrations of isoflavones are found in the starting beans (edamame) and foods derived from fermented beans (natto, tempeh, miso), while foods from the pressing of beans (tofu, soy milk) contain slightly less (Table 1). These foods are commonly consumed by Asians and allow them to obtain isoflavone intakes varying from 8 to 50 mg per day, depending on the region, quantities clearly greater than those of the inhabitants of Europe and America (less than 1 mg per day). It should be noted, however, that soy is gradually becoming more and more popular in the West as an alternative to meat and that isoflavone intake can reach levels similar to Asians (18–21 mg per day) in certain groups of health-conscious people.


Table 1. The isoflavone content of various foods.
Source: United States Department of Agriculture, Nutrient Data Laboratory.

FoodIsoflavone content
(mg/100 g)
Natto82.3
Tempeh
60.6
Soybeans (edamame)49.0
Miso41.5
Tofu22.1
Soy milk10.7

The importance of a high intake of isoflavones comes from the multiple biological properties of this class of molecules. In addition to their antioxidant and anti-inflammatory activities, common to many polyphenols, a unique feature of isoflavones is their structural resemblance to estrogens, the female sex hormones, and it is for this reason that these molecules are often referred to as phytoestrogens. This estrogenic action has so far been mainly studied in relation to the development of hormone-dependent breast cancers. Since the growth of these cancers is stimulated by estrogens, the presence of phytoestrogens creates a competition that attenuates the biological effects associated with these hormones, especially the excessive growth of breast tissue (this mode of action is comparable to that of tamoxifen, a drug prescribed for several years against breast cancer). It is also important to note that, contrary to a very widespread misconception, the consumption of soybeans should not be discouraged for women who have survived breast cancer. On the contrary, many studies conducted in recent years clearly show that regular soy consumption by these women is absolutely safe and is even associated with a significant decrease in the risk of recurrence and mortality from this disease. It should be mentioned that despite the similarity of isoflavones to estrogens, studies indicate that soy does not interfere with the effectiveness of tamoxifen or anastrozole, two drugs frequently used to treat hormone-dependent breast cancers. Consequently, for people who have been affected by breast cancer, there are only benefits to incorporating soy into their diet.

Several data suggest that the positive effect of isoflavones on health is not limited to their anticancer action, and that the combination of the antioxidant, anti-inflammatory and estrogenic activities of these molecules may also contribute to the cardiovascular benefits of soy (Table 2).


Table 2. Main properties of isoflavones involved in reducing the risk of cardiovascular disease associated with soy consumption.

Cardiovascular effectsProposed mechanisms
Vasodilation of blood vesselsIsoflavones interact with a subtype of estrogen receptor present in the coronary arteries (Erβ), leading to the production of nitrous oxide (NO), a gas that induces vasodilation of blood vessels.
Lower cholesterol levels
Accelerated elimination of LDL and VLDL in the liver.
Isoflavones reduce LDL-cholesterol oxidation in diabetic patients.
AntioxydantEquol, a metabolite of daidzein formed by the intestinal microbiome, has a strong antioxidant activity.
Anti-inflammatoryIsoflavones promote the establishment of an intestinal microbiome enriched with bacteria that produce anti-inflammatory molecules (Bifidobacterium spp., for example).

A cardioprotective effect associated with soy consumption is also suggested by the results of an epidemiological study recently published in Circulation. By examining the eating habits of 210,700 Americans (168,474 women and 42,226 men), the researchers found that people with the highest isoflavone intake (about 2 mg per day on average) had a risk of coronary heart disease decreased by 13% compared to those with minimal intake (0.15 mg per day on average). A protective effect is also observed for tofu, with an 18% reduction in the risk of coronary heart disease for people who consume it once or more per week compared to those who ate it very rarely (less than once per month). Regular consumption of soy milk (once or more per week) is also associated with a slight decrease in risk, but this decrease is not statistically significant.

These reductions may seem modest, but it should be noted that the amounts of soybeans consumed by participants in this study are relatively small, well below what is commonly measured in Japan. For example, in a Japanese study that reported a 45% decrease in the risk of myocardial infarction in women who consumed the most soy, the isoflavone intake of these people was on average around 40 mg/day, i.e. 20 times more than in the American study (2 mg/day). It is therefore likely that the reductions in the risk of coronary heart disease observed in the United States represent a minimum and could probably be greater as a result of higher soy intake.

An interesting aspect of the decreased risk of coronary heart disease associated with tofu is that it is observed as much in younger women before menopause as in postmenopausal women, but only if they are not using hormone therapy (Figure 3). According to the authors, it is possible that after menopause, the estrogenic action of isoflavones compensates for the drop in estrogen levels and may mimic the cardioprotective effect of these hormones. In the presence of synthetic hormones, on the other hand, isoflavones are “masked” by excess hormones and therefore cannot exert their beneficial effects. For younger women, it is likely that the higher expression of the estrogen receptor before menopause promotes a greater interaction with isoflavones and allows these molecules to positively influence the function of blood vessels.

Figure 3. Association between risk of coronary heart disease and tofu consumption by hormonal status.
From Ma et al. (2020).

Taken together, these observations suggest that soy products have a positive effect on cardiovascular health and therefore represent an excellent alternative to meat as a source of protein. A recent study reports that these cardiovascular benefits can be even more pronounced following the consumption of fermented soy products such as natto, which is very rich in isoflavones, but given its texture (sticky, gooey), its strong smell (reminiscent of a well-made cheese), and its low availability in grocery stores, this food is foreign to our food culture and unlikely to be adopted by the North American population. Tofu is probably the most accessible soy-derived food given its neutral taste that allows it to be used in a wide variety of dishes, Asian-style or not. Soy milk is a less attractive alternative, not only because its consumption is not associated with a significant decrease in the risk of coronary heart disease, but also because these products often contain significant amounts of sugar.

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.

 

Olive oil, the best source of fat for cooking

Olive oil, the best source of fat for cooking

OVERVIEW

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

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

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

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

A new metabolite derived from the microbiota linked to cardiovascular disease

A new metabolite derived from the microbiota linked to cardiovascular disease

OVERVIEW

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

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

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

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

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

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

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

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

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

Plant or animal proteins: An impact on health

Plant or animal proteins: An impact on health

OVERVIEW

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

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

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

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

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

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

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

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

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

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

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

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