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.

Choosing dietary sources of unsaturated fats has many health benefits

Choosing dietary sources of unsaturated fats has many health benefits

OVERVIEW

  • Unsaturated fatty acids, found mainly in vegetable oils, nuts, certain seeds and fatty fish, play several essential roles for the proper functioning of the human body.
  • While saturated fatty acids, found mainly in foods of animal origin, increase LDL cholesterol levels, unsaturated fats lower this type of cholesterol and thereby reduce the risk of cardiovascular events.
  • Current scientific consensus is therefore that a reduction in saturated fat intake combined with an increased intake of unsaturated fat represents the optimal combination of fat to prevent cardiovascular disease and reduce the risk of premature mortality.
Most nutrition experts now agree that a reduction in saturated fat intake combined with an increased intake of quality unsaturated fat (especially monounsaturated and polyunsaturated omega-3) represents the optimal combination of fat to prevent cardiovascular disease and reduce the risk of premature death. The current consensus, recently summarized in articles published in the journals Science and BMJ, is therefore to choose dietary sources of unsaturated fats, such as vegetable oils (particularly extra virgin olive oil and those rich in omega-3s such as canola), nuts, certain seeds (flax, chia, hemp) and fatty fish (salmon, sardine), while limiting the intake of foods mainly composed of saturated fats such as red meat. This roughly corresponds to the Mediterranean diet, a way of eating that has repeatedly been associated with a decreased risk of several chronic diseases, especially cardiovascular disease.

Yet despite this scientific consensus, the popular press and social media are full of conflicting information about the impact of different forms of dietary fat on health. This has become particularly striking since the rise in popularity of low-carbohydrate (low-carb) diets, notably the ketogenic diet, which advocates a drastic reduction in carbohydrates combined with a high fat intake. In general, these diets make no distinction as to the type of fat that should be consumed, which can lead to questionable recommendations like adding butter to your coffee or eating bacon every day. As a result, followers of these diets may eat excessive amounts of foods high in saturated fat, and studies show that this type of diet is associated with a significant increase in LDL cholesterol, an important risk factor for cardiovascular disease. According to a recent study, a low-carbohydrate diet (<40% of calories), but that contains a lot of fat and protein of animal origin, could even significantly increase the risk of premature death.

As a result, there is a lot of confusion surrounding the effects of different dietary fats on health. To get a clearer picture, it seems useful to take a look at the main differences between saturated and unsaturated fats, both in terms of their chemical structure and their effects on the development of certain diseases.

A little chemistry…
Fatty acids are carbon chains of variable length whose rigidity varies depending on the degree of saturation of these carbon atoms by hydrogen atoms. When all the carbon atoms in the chain form single bonds with each other by engaging two electrons (one from each carbon), the fatty acid is said to be saturated because each carbon carries as much hydrogen as possible. Conversely, when certain carbons in the chain use 4 electrons to form a double bond between them (2 from each carbon), the fatty acid is said to be unsaturated because it lacks hydrogen atoms.

These differences in saturation have a great influence on the physicochemical properties of fatty acids. When saturated, fatty acids are linear chains that allow molecules to squeeze tightly against each other and thus be more stable. It is for this reason that butter and animal fats, rich sources of these saturated fats, are solid or semi-solid at room temperature and require a source of heat to melt.

Unsaturated fatty acids have a very different structure (Figure 1). The double bonds in their chains create points of stiffness that produce a “crease” in the chain and prevent molecules from tightening against each other as closely as saturated fat. Foods that are mainly composed of unsaturated fats, vegetable oils for example, are therefore liquid at room temperature. This fluidity directly depends on the number of double bonds present in the chain of unsaturated fat: monounsaturated fats contain only one double bond and are therefore less fluid than polyunsaturated fats which contain 2 or 3, and this is why olive oil, a rich source of monounsaturated fat, is liquid at room temperature but solidifies in the refrigerator, while oils rich in polyunsaturated fat remain liquid even at cold temperatures.

Figure 1. Structure of the main types of saturated, monounsaturated and polyunsaturated omega-3 and omega-6 fats. The main food sources for each fat are shown in italics.

Polyunsaturated fats can be classified into two main classes, omega-3 and omega-6. The term omega refers to the locationof the first double bond in the fatty acid chain from its end (omega is the last letter of the Greek alphabet). An omega-3 or omega-6 polyunsaturated fatty acid is therefore a fat whose first double bond is located in position 3 or 6, respectively (indicated in red in the figure).

It should be noted that there is no food that contains only one type of fat. On the other hand, plant foods (especially oils, seeds and nuts) are generally made up of unsaturated fats, while those of animal origin, such as meat, eggs and dairy products, contain more saturated fat. There are, however, exceptions: some tropical oils like palm and coconut oils contain large amounts of saturated fat (more than butter), while some meats like fatty fish are rich sources of omega-3 polyunsaturated fats such as eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids.

Physiological roles of fatty acids
All fatty acids, whether saturated or unsaturated, play important roles in the normal functioning of the human body, especially as constituents of cell membranes and as a source of energy for our cells. From a dietary point of view, however, only polyunsaturated fats are essential: while our metabolism is capable of producing saturated and monounsaturated fatty acids on its own (mainly from glucose and fructose in the liver), linoleic (omega-6) and linolenic (omega-3) acids must absolutely be obtained from food. These two polyunsaturated fats, as well as their longer chain derivatives (ALA, EPA, DHA), play essential roles in several basic physiological functions, in particular in the brain, retina, heart, and reproductive and immune systems. These benefits are largely due to the degree of unsaturation of these fats, which gives greater fluidity to cell membranes, and at the same time facilitate a host of processes such as the transmission of electrical impulses in the heart or neurotransmitters in the synapses of the brain. In short, while all fats have important functions for the functioning of the body, polyunsaturated fats clearly stand out for their contribution to several processes essential to life.

Impacts on cholesterol
Another major difference between saturated and unsaturated fatty acids is their respective effects on LDL cholesterol levels. After absorption in the intestine, the fats ingested during the meal (mainly in the form of triglycerides and cholesterol) are “packaged” in structures called chylomicrons and transported to the peripheral organs (the fatty tissue and the muscles, mainly) where they are captured and used as a source of energy or stored for future use. The residues of these chylomicrons, containing the portion of excess fatty acids and cholesterol, are then transported to the liver, where they are taken up and will influence certain genes involved in the production of low-density lipoproteins (LDL), which serve to transport cholesterol, as well as their receptors (LDLR), which serve to eliminate it from the blood circulation.

And this is where the main difference between saturated and unsaturated fats lies: a very large number of studies have shown that saturated fats (especially those made up of 12, 14 and 16 carbon atoms) increase LDL production while decreasing that of its receptor, with the result that the amount of LDL cholesterol in the blood increases. Conversely, while polyunsaturated fats also increase LDL cholesterol production, they also increase the number and efficiency of LDLR receptors, which overall lowers LDL cholesterol levels in the blood. It has been proposed that this greater activity of the LDLR receptor is due to an increase in the fluidity of the membranes caused by the presence of polyunsaturated fats which would allow the receptor to recycle more quickly on the surface liver cells (and therefore be able to carry more LDL particles inside the cells).

Reduction of the risk of cardiovascular disease
A very large number of epidemiological studies have shown that an increase in LDL cholesterol levels is associated with an increased risk of cardiovascular diseases. Since saturated fat increases LDL cholesterol while unsaturated fat decreases it, we can expect that replacing saturated fat with unsaturated fat will lower the risk of these diseases. And that is exactly what studies show: for example, an analysis of 11 prospective studies indicates that replacing 5% of caloric intake from saturated fat with polyunsaturated fat was associated with a 13% decrease in the risk of coronary artery disease. A similar decrease has been observed in clinical studies, where replacing every 1% of energy from saturated fat with unsaturated fat reduced the risk of cardiovascular events by 2%. In light of these results, there is no doubt that substituting saturated fats with unsaturated fats is an essential dietary change to reduce the risk of cardiovascular disease.

A very important point of these studies, which is still poorly understood by many people (including some health professionals), is that it is not only a reduction of saturated fat intake that counts for improving the health of the heart and vessels, but most importantly the source of energy that is consumed to replace these saturated fats. For example, while the substitution of saturated fats by polyunsaturated fats, monounsaturated fats or sources of complex carbohydrates like whole grains is associated with a substantial reduction in the risk of cardiovascular disease, this decrease is completely abolished when saturated fats are replaced by trans fats or poor quality carbohydrate sources (e.g., refined flours and added sugars) (Figure 2). Clinical studies indicate that the negative effect of an increased intake of simple sugars is caused by a reduction in HDL cholesterol (the good one) as well as an increase in triglyceride levels. In other words, if a person decreases their intake of saturated fat while simultaneously increasing their consumption of simple carbohydrates (white bread, potatoes, processed foods containing added sugars), these sugars simply cancel any potential cardiovascular benefit from reducing saturated fat intake.


Figure 2. Modulation of the risk of coronary heart disease following a substitution of saturated fat by unsaturated fat or by different sources of carbohydrates. The values shown correspond to variations in the risk of coronary heart disease following a replacement of 5% of the caloric intake from saturated fat by 5% of the various energy sources. Adapted from Li et al. (2015).

Another implication of these results is that one should be wary of “low-fat” or “0% fat” products, even though these foods are generally promoted as healthier. In the vast majority of cases, reducing saturated fat in these products involves the parallel addition of simple sugars, which counteracts the positive effects of reducing saturated fat.

This increased risk from simple sugars largely explains the confusion generated by some studies suggesting that there is no link between the consumption of saturated fat and the risk of cardiovascular disease (see here and here, for example). However, most participants in these studies used simple carbohydrates as an energy source to replace saturated fat, which outweighed the benefits of reduced intake of saturated fat. Unfortunately, media coverage of these studies did not capture these nuances, with the result that many people may have mistakenly believed that a high intake of saturated fat posed no risk to cardiovascular health.

In conclusion, it is worth recalling once again the current scientific consensus, stated following the critical examination of several hundred studies: replacing saturated fats by unsaturated fats (monounsaturated or polyunsaturated) is associated with a significant reduction in the risk of cardiovascular disease. As mentioned earlier, the easiest way to make this substitution is to use vegetable oils as the main fatty substance instead of butter and to choose foods rich in unsaturated fats such as nuts, certain seeds and fatty fish (salmon, sardine), while limiting the intake of foods rich in saturated fats such as red meat. It is also interesting to note that in addition to exerting positive effects on the cardiovascular system, recent studies suggest that this type of diet prevents excessive accumulation of fat in the liver (liver steatosis), an important risk factor of insulin resistance and therefore type 2 diabetes. An important role in liver function is also suggested by the recent observation that replacing saturated fats of animal origin by mono- or polyunsaturated fats was associated with a significant reduction in the risk of hepatocellular carcinoma, the main form of liver cancer. Consequently, there are only advantages to choosing dietary sources of unsaturated fat.

Spicing up the prevention of cardiovascular disease with chili peppers

Spicing up the prevention of cardiovascular disease with chili peppers

OVERVIEW

  • The frequency of weekly consumption of chili peppers by 22,811 Italians from the Molise region was measured over an 8-year period.
  • At the same time, researchers identified deaths from cardiovascular disease, cancer or other causes that occurred during this period.
  • Results show that people who eat chilies 4 or more times per week have a 44% and 61% reduced risk of death from myocardial infarction or stroke, respectively, compared to those who never or very rarely eat them.

Chili peppers (Capsicum spp.) are native to South America, where they were already being cultivated for culinary purposes more than 6,000 years ago. Following the discovery of America by Europeans in the 15th century, these hot peppers were disseminated worldwide by Portuguese sailors (particularly in India and Asia), where they were quickly adopted and became essential ingredients in the culinary cultures of these countries.

The gastronomic value of chilies obviously comes from their spicy flavour, which distinctively enhances the taste of different dishes. This property is due to the presence of capsaicin (Figure 1), a phenolic compound that specifically interacts with certain receptors (TRPV1 for Transient Receptor Potential Vanilloid) involved in the pain signal generated by temperatures above 43ºC.

Figure 1. Molecular structure of capsaicin, the molecule responsible for the spicy taste of chili peppers.

By binding to the TRPV1 receptor present in the mouth, capsaicin therefore causes a feeling of heat or a burning sensation, which completely tricks the brain into believing that the mouth is literally “on fire”. The reason many people are attracted to these “painful” substances is still not understood, but could be related to the release of pleasure molecules (endorphins) to mitigate the effects of the “burn” detected by the brain.

In addition to their unique taste properties, a recent study suggests that chili peppers may have positive health effects, particularly for cardiovascular disease. Over an 8-year period, researchers followed just over 20,000 people recruited into the Moli-sani Project, a prospective study of residents of the Molise region of southeastern Italy. By analyzing deaths during this period according to the frequency of chili pepper consumption by participants, the researchers found that the risk of dying prematurely from all causes was reduced by 23% for hot pepper lovers (consumption 4 times per week). This decrease was particularly apparent for mortality linked to coronary heart disease (44%) and cerebrovascular disease (61%) (Figure 2). A downward trend was observed for cancer mortality, but the difference is not statistically significant.

Figure 2. Reduced risk of all-cause mortality and mortality related to various diseases among regular chili pepper consumers. Adapted from Bonaccio et al. (2019). N.S., not significant.

These observations are in agreement with previous studies that have observed a significant reduction (approximately 10–20%) of premature mortality among the largest consumers of spicy foods (here and here, for example).

As the editorial accompanying the article points out, although this type of population study does not directly establish a causal link between chili pepper consumption and mortality, it remains that the experimental data accumulated in recent years make this link biologically plausible. On the one hand, several studies have suggested that capsaicin may help prevent the development of obesity, an important risk factor for diabetes and cardiovascular disease. For example, epidemiological studies have observed that regular consumption of these peppers is associated with a reduction in the prevalence of obesity in certain populations, and clinical studies have observed a loss of abdominal fat following the administration of a supplement of capsinoids (capsaicin and related molecules) compared to placebo. This positive effect of capsaicin on body weight maintenance is mainly linked to a decrease in calorie intake, caused by decreased appetite and increased satiety.

On the other hand, it should be noted that capsaicin also influences other phenomena linked to an increased risk of cardiovascular disease, notably by improving the response to insulin, reducing the oxidation of low-density lipoproteins (LDL), and improving endothelial function. Studies have also suggested that people who season their food with hot peppers eat less salt and are less at risk for hypertension, the main risk factor for cardiovascular events.

Overall, these observations raise the interesting possibility that some minor dietary changes, such as the addition of chili peppers, may have positive impacts on health, particularly at the cardiovascular level. Of course, there should be no illusions: if a person’s diet is based on ultra-processed foods and contains very little fruit and vegetables, it is not by adding sriracha sauce or Tabasco that they will manage to decrease their risk of cardiovascular disease. But in the context of a diet known to be positive for the health of the heart and vessels, such as the Mediterranean diet (adopted by most of the participants of the study mentioned above), it is possible that the positive biological effects of chili peppers on body weight, blood sugar and reduced salt intake may accentuate the benefits associated with this diet and therefore have a positive impact on health.

Anti-aging effect of a healthy lifestyle

Anti-aging effect of a healthy lifestyle

According to recent studies, adopting a healthy lifestyle, i.e., eating well, exercising, managing stress, and not smoking or drinking too much alcohol, has beneficial effects on the aging of our cells. One of the well-documented phenomena that occur during cellular aging is the degradation of telomeres, unique structures found at the ends of each of our chromosomes; however, a healthy lifestyle can slow down this process

Telomeres and aging
Telomeres are repetitive DNA structures, shaped like a “hairpin”, found at both ends of chromosomes and that ensure the integrity of the genome during cell division. At each division, the telomeres shorten until they become too short to fulfill their protective function: the cell can no longer divide and enters senescence, then dies. Telomere shortening is countered by the action of telomerase, an enzyme that lengthens telomeres during each DNA replication. Telomere shortening in peripheral blood mononuclear cells (lymphocytes and monocytes) is associated with aging and aging-related diseases such as cancer, stroke, dementia, cardiovascular disease, obesity, osteoporosis and type 2 diabetes. Leukocyte telomere length is significantly, albeit weakly, associated with mortality, but cannot predict survival as well as other variables (age, mobility, cognition, smoking, daily life activities).

Physical activity
Physical training improves many aspects of human health, including exercise capacity, blood pressure regulation, insulin sensitivity, lipid profile, reduction of abdominal fat and inflammation. These beneficial effects contribute to increased endothelial function, delay the progression of atherosclerotic lesions, and improve collateralization of blood vessels in people with type 2 diabetes, coronary artery disease and heart failure. The underlying mechanisms are known in part, but details at the molecular level are less well known and are the subject of much research.

The process of cellular aging can be slowed down by sustained exercise. A study published in 2009 showed that sustained physical training in young and middle-aged athletes was associated with higher telomerase activity, increased expression of telomere-stabilizing proteins, and longer telomeres, compared to sedentary people.

The same research group recently conducted a randomized controlled trial to demonstrate that exercise is the cause of increased telomerase activity and telomere length. The results of the study were published in 2018 in the European Heart Journal. The researchers recruited 124 middle-aged men and women (≈50 years) who were in good health, but did not exercise. During the six-month study, participants were randomly divided into four groups: a control group and three groups that did different types of exercise 3 times a week; one group did endurance training (walking/running, 45 min/day); another group exercised at high intensity intervals (4 min at high intensity/4 min rest, repeated 4 times); and the third group did resistance exercises (various weight machines). Blood samples were taken before, during, and at the end of the study to measure telomere length and telomerase activity in leukocytes (white blood cells).

At the end of the study, those who exercised, regardless of the type, had better cardiorespiratory capacity than at the beginning of the study. Telomerase activity was 2–3 times higher in the leukocytes of those who did endurance or interval exercises, compared to the control group. However, this effect was not observed in people who did resistance exercises (weight training). Similarly, telomere length was greater in those who did endurance or interval exercises, but not in those who did resistance exercise.

These results suggest that endurance exercises such as running, brisk walking or swimming are more effective than resistance exercises to keep longer telomeres and delay cellular aging. It should not be concluded, however, that resistance exercises are useless for healthy aging. Resistance exercises increase overall fitness, which is one of the most important indicators of longevity. The researchers suggest further study on the effects of various combinations of endurance and resistance exercises on cellular aging. The lead author concludes that the central message of his study is that it is never too late to start exercising and that it will have beneficial effects on aging.

Proteomic approach to the effects of exercise
Researchers have studied the effects of endurance exercise on the expression of 1,129 proteins in the blood plasma (plasma proteome), classified into 10 modules or patterns according to their level of interconnection. Exercise altered protein expression of four modules in young men, and five modules in older men. Modules affected by the exercise included proteins related to signalling pathways involved in wound healing, apoptosis (cell death) regulation, glucose, insulin and cellular stress signalling, as well as immune and inflammatory responses. In addition, several exercise-affected modules could be correlated with physiological and clinical indicators of a healthy life, including diastolic blood pressure, insulin resistance, maximal aerobic capacity, and vascular endothelial function.

Diet
According to a systematic review of studies published on the subject, five studies indicate that fruit and vegetable consumption is associated with longer telomeres, while eight other studies have not identified a significant association. For foods other than fruits and vegetables, including grains and meats, the data are inconclusive as a whole. Some studies, however, indicate unfavourable associations between certain food groups and the length of telomeres: grains, processed meats, sugary drinks, fats and oils. With regard to eating habits, only the Mediterranean diet has been associated with longer telomeres, but not in all the studies published to date. Future larger-scale observational studies and more focused randomized controlled trials could help to better identify which elements of the diet are beneficial for telomere maintenance and help slow the process of cellular aging.

Effect of stress
Several cross-sectional studies have reported associations between telomere stability and stress exposure (review articles here, here and here). The association lasts throughout life and has been observed in children whose mothers had been under significant stress. It seems that even prenatal stress indirectly experienced by the fœtus is associated with shorter telomeres after birth. Prolonged or repeated exposure to stress is associated with a shortening of telomeres and the development of age-related diseases such as type 2 diabetes, heart disease, dementia and osteoarthritis. According to some studies, people with bipolar disorder, schizophrenia, major depression and post-traumatic stress disorder have shorter telomeres. Stress and mental illnesses therefore have direct effects on the aging of our cells, with consequences for health over the course of life.

Global lifestyle
For men diagnosed with low-grade prostate cancer, adopting a completely different and healthy lifestyle (plant-based, low-fat diet, exercise, stress management, social support) has been associated with a 10% increase in telomere length in their lymphocytes and monocytes, five years after the start of the intervention. Participants in the control group (active surveillance only), on the contrary, saw the average length of their telomeres decrease slightly (-3%). This intervention study included only a small group of people (n = 30), so larger-scale randomized controlled trials are needed to confirm these findings.

There is growing evidence that physical activity has a significant influence on health and quality of life as people age. For example, older people who exercise regularly are often in better shape, they are more muscular, and they are less likely to develop chronic illnesses or physical disabilities than sedentary seniors. Adopting a lifestyle that combines healthy eating, regular exercise and stress management is certainly one of the best things one can do to prevent or fight age-related diseases.

The effects of nitrates and nitrites on the cardiovascular system

The effects of nitrates and nitrites on the cardiovascular system

Updated May 23, 2018

Nitrates (NO3) and nitrites (NO2) are mostly known to the public as undesirable residues of the agri-food chain as they are associated with potentially carcinogenic effects. Yet, these molecules are naturally found in fruits and vegetables (nitrates) as well as in the human body (nitrates and nitrites) where they contribute to important physiological functions, particularly in the cardiovascular system. Moreover, it has now been proven that dietary nitrates can be beneficial to cardiovascular health and sports performance, as will be discussed below.

Nitrates and Nitrites: Dangerous or Harmless?

During the curing process used to transform meats into charcuterie (ham, sausages, bacon, etc.), nitrite salt is added to stabilize the colour and taste of meats and to prevent the development of pathogenic microorganisms. Nitrite salt is in fact very effective in preventing the proliferation of bacteria, including the formidable Clostridium botulinum, which produces a powerful toxin that causes botulism, a very serious, sometimes deadly, paralytic illness. Nitrates and nitrites themselves are not carcinogenic; rather, it is N-nitroso compounds, such as nitrosamines, produced by the reaction between nitrites and meat protein that are. The curing process promotes the formation of nitrosamines due to the abundance of added nitrites, proteins and myoglobin whose heme group accelerates the reaction. Cooking at high temperatures (deep-frying) greatly accelerates the formation of nitrosamines. Government regulations limit the quantity of nitrites used to cure meats and requires the addition of neutralizing agents (antioxidants) in certain products, for example bacon. Nitrates naturally present in food mainly come from fruits and vegetables, which contain antioxidants, such as vitamin C and polyphenols that prevent the formation of N-nitroso compounds.

Up until about twenty years ago, nitrates and nitrites found in the human body were considered inert final products of the metabolism of nitric oxide (NO), a gas that acts as a signalling molecule and contributes to the regulation of blood flow and several other physiological functions. In the presence of oxygen, nitric oxide is produced in the endothelial cells that line blood vessels through the oxidizing reaction of the amino acid L-arginine into NO and L-citrulline. Several medications used to treat heart disease increase the signalling pathway of NO, either by increasing its bioavailability or by inhibiting its degradation. The most well-known are organic nitrates (e.g. nitroglycerine). They act by releasing NO rapidly and induce non-specific dilatation of both arteries and veins, which improves blood flow. Other pharmacological agents are phosphodiesterase-5 inhibitors, which are used to treat pulmonary hypertension and erectile dysfunction (e.g. sildenafil, better known by the brand name Viagra). Moreover, inhibitors of the HMG reductase enzyme (statins) and of the angiotensin-converting enzyme indirectly increase the bioavailability of NO.

Since 2001, we know that endogenous nitrites are an important alternative source of NO, particularly when oxygen levels are low, as is the case with blood microcirculation (see Figure 1). At that time, it was thought that the intake of nitrates and nitrites from food sources had no effect on blood vessels, since it was not thought that this intake could increase the circulating concentration of nitrites. We now know that dietary nitrates are quickly absorbed in the small intestine, about 75% of nitrates are excreted by the kidneys, and what is left becomes highly concentrated in the salivary glands (10 times the plasma concentration). When nitrates are secreted in saliva, they are converted to nitrites by the commensal bacteria, then swallowed with the saliva and absorbed into intestinal circulation. The circulating nitrites can be transformed into nitric oxide by different enzymes (reductases).

Figure 1. Formation and recycling of nitrates (NO3), nitrites (NO2) and nitric oxide (NO). Adapted from Woessner et al., 2017. In the presence of oxygen, endothelial nitric oxide synthase (eNOS) catalyzes the oxidation of L-arginine to NO. NO can also be quickly oxidized into nitrites and nitrates. A secondary source of vascular NO is obtained through diet. Consumption of foods high in inorganic nitrates (green leafy vegetables, beetroot) has been shown to increase plasma nitrate concentration,which can be secreted in saliva and reduced to nitrite by commensal bacteria in the mouth. Nitrites can then be further reduced to NO (and other biologically active nitrogen oxides) via several mechanisms that are expedited under hypoxic conditions. Hence, although some of the circulating nitrates and nitrites are excreted in the kidneys, they can also be recycled back to NO.

Dietary Sources of Nitrates
About 85% of dietary nitrates (NO3) come from vegetables, and the rest mostly from drinking water. Dietary nitrites (NO2) mostly come from cured meats (charcuterie). Vegetables can be grouped into 3 categories according to their nitrate content (see Table I). Vegetables high in nitrates (>1000 mg/kg) belong to the Brassicaceae (arugula), Chenopodiaceae (beetroot, spinach), Asteraceae (lettuce), and Apiaceae (celery) families. Most commonly eaten vegetables have medium levels of nitrates (100–1000 mg/kg), whereas onions and tomatoes contain very little nitrates (<100 mg/kg). Juicing vegetables is a popular and convenient way to increase vegetable consumption, and several commercial juices are available on the market. Whereas the nitrate content of homemade fresh juice is negligible, it increases dramatically after two days at room temperature, but remains low if stored in the refrigerator at 4 °C. The conversion of nitrates to nitrites in juices prepared at home is due to the presence of bacterial enzymes (reductases), which is less problematic in commercially prepared juices since they are lightly pasteurized.

Table I. Nitrate content in vegetables and water. Source: Lidder & Webb, 2012.

*Note: To facilitate the selection of vegetables to build a diet, the authors recommend using “nitrate units” (1 unit = 1 mmol) to ensure sufficient nitrate intake in order to benefit from the hypotensive effects or to improve exercise performance, and also to avoid consuming more nitrates than recommended (4.2 units for an adult weighing 70 kg).

The acceptable daily intake (ADI) established by the European Food Safety Authority for nitrates is 3.7 mg/kg (0.06 mmol/kg), which corresponds to about 260 mg (4.2 mmol) daily for an adult weighing 70 kg. This ADI was established by dividing the maximum harmless dose for rats and dogs by 100. According to estimations, Europeans consume 31–185 mg of nitrates daily and 0–20 mg of nitrites daily. Based on the moderate recommendation to eat 400 g of a variety of fruits and vegetables per day, the dietary intake of nitrates is about 157 mg/day. Several countries currently recommend a diet high in nitrates for people with heart disease. The DASH diet (Dietary Approach to Stop Hypertension), for example, with its emphasis on fruits and vegetables, whole grains, lean meats (poultry, fish) and nuts, provides a significant level of nitrates. In a clinical study, the DASH diet (rich in fruits and vegetables) lowered blood pressure in subjects with hypertension almost as much as a monotherapy with antihypertensive medication. In fact, it has been suggested that the cardioprotective effects of fruits and vegetables observed in epidemiological studies are caused by the high nitrate content of green leafy vegetables.

The choice of fruits and vegetables eaten can have an important impact on the quantity of dietary nitrates. For example, it is estimated that a DASH diet that only includes fruits and vegetables with low nitrate levels would provide 174 mg of nitrates and 0.41 mg of nitrites, whereas choosing fruits and vegetables high in nitrates can provide up to 1222 mg of nitrates and 0.35 of nitrites. This estimation indicates that the dietary intake of nitrates can vary up to about 700%, according to dietary choices. An excessive intake of nitrates, which is very rare, can cause methemoglobinemia, a disease or intoxication where the level of methemoglobin (a type of hemoglobin that cannot bind oxygen) is too high. Infants (<3 years) are much more susceptible than older children and adults to this disease. In children it is sometimes called “blue baby syndrome.” In adults, this intoxication is rare because their diet cannot contain nitrates in high enough quantities to cause the disease. However, infants can get sick by consuming 200 g of spinach high in nitrates/per day. The American Academy of Pediatrics recommends not giving children foods (purees) containing vegetables (e.g. spinach, beetroot, green beans, carrots) before the age of three months.

A prospective study published in 2018 revealed an association between urinary nitrate and the prevalence of heart disease and the risk of mortality. A concentration of nitrates in urine that was 10 times higher was associated with a 33% decreased risk of hypertension and a 39% decreased risk of stroke. However, there was no association between the concentration of nitrates in urine and the risk of myocardial infarction. Moreover, a ten-fold increase of urinary nitrates was associated with a reduction in all-cause mortality (–37%) and a reduction in cardiovascular mortality (–56%). Despite concerns that nitrates can be converted to nitrites and N-nitrosamines and become carcinogenic, nitrates in urine were not associated with cancer prevalence or cancer mortality. Future studies should evaluate whether nitrate supplements can prevent or reduce the prevalence of heart disease and premature death.

The Effect of Nitrates on Blood Pressure
study published in 2008 (randomized, placebo-controlled, crossover design) evaluated the effects of a diet high in nitrates on blood pressure in healthy, non-smoking and physically active participants. A diet high in nitrates led to a significant decrease in average blood pressure (3.2 mm Hg) and diastolic blood pressure (3.7 mm Hg), when compared to a diet low in nitrates. In this study, the daily dose of nitrate supplements taken corresponded to that normally contained in 150–250 g from vegetables high in nitrates, such as spinach, beetroot and lettuce. The authors note that the decrease in blood pressure observed in their study was similar to that observed in the DASH study in the healthy group that ate a diet rich in fruits and vegetables, when compared with the group that consumed few fruits and vegetables. In another study, drinking 500 ml of beetroot juice led to an even more significant decrease in systolic (~10.4 mm Hg) and diastolic (~8 mm Hg) blood pressure, when compared to the group that ingested the placebo (500 ml of water, crossover study). This effect was temporally correlated with the transient increase in plasma nitrite concentration. Interrupting the enterosalivary conversion cycle of nitrates to nitrites (by asking participants to spit out all their saliva for 3 hours after ingesting beetroot juice) completely prevented the increase of plasma nitrite concentration, and the decrease in blood pressure. This latter finding confirms that the decrease in blood pressure caused by the consumption of beetroot juice is due to the conversion of nitrates found in beetroot juice to nitrites.

Hypertension, Type 2 Diabetes, Hypercholesterolemia, Obesity
Even though the effect of nitrates on the decrease in blood pressure in healthy subjects was consistently reported in several studies, this is not always the case in studies among subjects with a chronic disease. In a British study of 68 subjects with hypertension, the blood pressure of those who drank 250 ml of beetroot juice daily for a month was lower by 8 mm Hg, compared to those who consumed beetroot juice depleted of nitrates (placebo). In a similar study, also among hypertensive subjects, no decrease in blood pressure was observed, even though the consumption of beetroot juice resulted in a considerable increase in plasma nitrite concentration. In another study of diabetics, there were no effects of dietary nitrites (beetroot juice) on blood pressure, endothelial function, and insulin sensitivity. However, supplementing the diet with beetroot juice significantly reduced systolic blood pressure of overweight or obese participants, aged 55 to 70, when compared to supplementation with blackcurrant juice, which was very low in nitrates. Finally, a study among 69 participants with hypercholesterolemia showed that the intake of dietary nitrates improved vascular function when compared to the group that received the placebo. The reason for variability of the results obtained in these clinical studies is unknown. Length of the treatment, medications used to manage hypertension, methods used to measure blood pressure, and differences between cohorts (e.g. age, BMI, diminished response to NO in certain diseases) are among possible explanatory factors.

Heart Failure
recent study (randomized, placebo-controlled, crossover design) shows that dietary nitrate supplementation (beetroot juice) increases exercise performance in people with heart failure with reduced ejection fraction. Here is a summary of the study and the main results. After consuming 140 ml of concentrated beetroot juice, the plasma nitrate and nitrite concentration of subjects increased on average by 15 times (1469%) and 2 times (105%), respectively, and the concentration of nitric oxide (a gas) in breath increased by 60%. This effect was not observed with the placebo, a beetroot juice previously depleted of nitrates and that could not be differentiated from the original beetroot juice (packaging, colour, texture, taste and smell) by the study subjects. Two hours after consuming the beetroot juice, subjects exercised for a few minutes on an ergometer stationary bike in a semi-reclined position at various intensities. Respiratory gas exchange was measured continuously. Heart rate, blood pressure and perceived fatigue were evaluated during the last 30 seconds of each phase. Consumption of nitrates had no effect on the ventilatory response, or exercise efficiency, heart rate, and blood pressure. However, compared to the placebo group, the subjects that ingested the beetroot juice were able to reach peak oxygen consumption (VO2 peak) that was higher by 8%, and increased, on average, their duration of effort to exhaustion by 7%. These findings suggest that dietary nitrate intake could be a valuable addition to the management of exercise intolerance among patients with heart failure with reduced ejection fraction.

Nitrates and Athletic Performance
Several studies have been conducted on the impact of nitrate supplementation on the performance of amateur and competitive athletes. In one study, 10 young men drank concentrated beetroot juice or a placebo and, after 2.5 hours (to coincide with the maximum concentration of circulating nitrites), did moderate to high intensity physical activity. When compared to the placebo group, consuming 70 ml of beetroot juice had no effect on athletic performance, but ingesting 140 ml or 280 ml of juice reduced oxygen consumption during moderate physical activity by 1.7% and 3.0%, whereas average time–to-task failure(at very high intensity) increased from 8 min 18 s to 9 min 30 s (14%) and from 8 min 13 s to 9 min 12 s (12%), respectively. Such an increase (12–14%) can seem enormous, but in fact translates to about a 1 to 2% reduction in time to complete a race, for example. In an elite sport, a 1% difference is considered very significant, reducing the time it takes to race a 1,500-metre distance by about 2 seconds and that of a 3,000-metre distance by about 4–5 seconds, for example. Other studies have shown a reduction in oxygen consumption (for the same effort) and an improvement in performance for walking, running, rowing, and cycling, through nitrate supplementation (beetroot juice or NaNO3). A meta-analysis of 17 of these studies shows that nitrates give a small advantage in performance for time to exhaustion tests, and have a slight beneficial, but not statistically significant, effect on performance during time trials. Another meta-analysis, published in 2016, including 26 randomized, placebo-controlled studies, indicates that nitrate supplementation significantly reduces oxygen consumption for a given effort during a moderate to high intensity exercise in healthy individuals, but not in people with a chronic disease.

Beetroot juice and other supplements with high nitrate levels are obviously not a cure-all. It is better to adopt a global approach to stay healthy, i.e. exercise daily and follow a healthy diet (Mediterranean for example) and eat several servings of fruits and vegetables every day, including green vegetables rich in nitrates, fibre, minerals and vitamins.

The Blue Zones: Areas where people are living better and longer

The Blue Zones: Areas where people are living better and longer

Updated on March 15, 2019

Life expectancy at birth in Canada in 2015 was 84.1 years for women and 80.2 years for men. It has been steadily rising for half a century: in 1960 life expectancy was 74.1 years for women and 71.1 for men. However, it is far from the exceptional longevity observed in specific areas of our planet where we find a large proportion of centenarians. These regions, named “Blue Zones”, have been identified by two demographers, Gianni Pes and Michel Poulain, and journalist Dan Buettner, author of the article The Secrets of Long Life in National Geographic magazine and the book The Blue Zones.

The five Blue Zones identified in the world.


Sardinia, Italy
By studying the longevity of the inhabitants of Sardinia, an Italian island in the Mediterranean Sea, the demographers Gianni Pes and Michel Poulain and their collaborators have located the areas where morecentenarianslive. These longevity hot spots, or Blue Zones (the researchers initially used a blue marker to delineate these areas on a map), are located in a mountainous area of ​​the island, the Barbagia, which was still difficult to access a few decades ago. This geographical situation discouraged immigration and promoted consanguinity, reducing the diversity of the genetic heritage. In the area of ​​exceptional longevity, in the southeast of the Province of Nuoro, 91 people have become centenarians among the 18,000 people who were born in the region between 1880 and 1900. In one village in particular, Seulo, 20 centenarians were identified between 1996 and 2016. In comparison, according to Statistics Canada, there were 17.4 centenarians per 100,000 inhabitants in Canada in 2011.

The analysis of genes involved in inflammation, cancer and heart disease did not reveal any significant difference that could be related to the exceptional longevity of the Sardinians. Researchers therefore suspect that environmental characteristics, lifestyle and diet are much more important than genetic predispositions for a long and healthy life. Many of these Sardinian centenarians are shepherds or farmers who have been doing a great deal of outdoor physical activity throughout their lives. The Sardinian diet, which is part of the Mediterranean diet, could play an important role in the longevity of the inhabitants of this Blue Zone. Indeed, the Sardinian diet consists of homegrown vegetables (mainly beans, tomatoes, eggplants), whole-grain bread, Pecorino cheese made from whole milk from grass-fed sheep, and local red wine particularly rich in polyphenols. The traditional Sardinian diet included meat once a week at most.

When journalist Dan Buettner asked some of these centenarians the reason for their exceptional longevity, many mentioned the importance of family and social ties; in Sardinia, elderly people live with their family rather than in retirement homes. The elderly who live in the Sardinian Blue Zone believe they have excellent mental well-being and report few symptoms of depression. An Italian study of 160 elders of the Sardinian Blue Zone reports that the trait of resilience was significantly associated with markers of good mental health. For these seniors, resilience and satisfaction derived from social ties are predictors of all markers of good mental health.

Okinawa, Japan
Japan has one of the largest concentrations of centenarians in the world, more than 34.7 per 100,000 inhabitants in 2010. The inhabitants of the islands of the Okinawa archipelago in southwestern Japan have a particularly high life expectancy, and 66.7 centenarians per 100,000 inhabitants have been recorded in this prefecture. Women living in Okinawa are 3 times more likely to live to age 100 than North Americans. The Okinawa diet is plant-based, and includes many leafy green vegetables, sweet potatoes, fish and seafood. The majority of Okinawa’s centenarians maintained a vegetable garden during their lifetime and moderate physical activity, which helps reduce stress and stay in shape. The people of Okinawa traditionally practice self-restraint when it comes to food, by following the Confucian teaching hara hachi bu, which recommends eating so as to be 80% satiated at the end of a meal. Older people in Okinawa are very active and maintain strong family and social ties, for example through regular meetings called moai. It is very important for them to make sense of their life. To have an ikigaiis to have a reason to get up every morning.

Nicoya, Costa Rica
Life expectancy is relatively high in Costa Rica (82.1 for women and 77.4 for men), especially in the region of the Nicoya Peninsula where men aged 60 are 7 times more likely to become centenarians than other Costa Ricans. Like Sardinia, Nicoya is a region that has been relatively isolated for hundreds of years. The cancer mortality rate is 23% lower than in the rest of the country, and Nicoya residents have a plant-based diet (squash, black beans, corn tortillas, plenty of local fruits), but that also includes eggs and meat (chicken and pork). The centenarians of Nicoya are very physically active, have strong family ties as well as strong religious faith, and like to work. Their stress level is low and they are generally very positive and happy.

Loma Linda, United States
The only identified Blue Zone in North America is located in Loma Linda, a city in Southern California, located 100 km east of Los Angeles, where there is a community of 9,000 members of the Seventh-day Adventist Church. In California, a 30-year-old Adventist man will live on average 7.3 years longer than a white Californian of the same age. A 30-year-old Adventist woman will live on average 4.4 years longer than a Californian of the same age. Knowing that about two thirds of Americans die from cardiovascular disease or cancer, it is not surprising that Adventists are living longer as their way of life means they are less at risk of developing these diseases. About half of Adventists are vegetarians or rarely eat meat, and non-vegetarian Adventists are twice as likely to develop cardiovascular disease. The majority of Adventists are non-smokers and do not drink alcohol. As a result, they have a lower incidence of lung cancer than Americans in general. Adventists are physically active and have a very developed community spirit, as they are very religious and their church encourages its members to help one another.

Icaria, Greece
Icaria is a Greek island in the Eastern Aegean Sea where one in three inhabitants will reach the age of 90. The incidence of cancer, cardiovascular disease, diabetes and dementia is significantly lower than the rest of the world. As in Sardinia, Okinawa and other Blue Zones, Icarians maintain a vegetable garden at home and lead a low-stress life. Their diet, of the Mediterranean type, is composed of vegetables (potatoes, peas, lentils, green leafy vegetables), fruits, olive oil, fish, goat milk, dairy products, and a little meat. Icarians eat little sugar and drink coffee, red wine and herbal teas made from rosemary, sage, oregano and artemisia daily. Icarians who observe the calendar of the Greek Orthodox Church must fast regularly, and caloric restriction is known to slow down the aging process in mammals.

The inhabitants of the Blue Zones, Okinawa, Sardinia, Nicoya, Icaria and Loma Linda, share characteristics in their lifestyle that contribute to their longevity. In his book The Blue Zones, Dan Buettner lists 9 common features:

    • Moderate and regular physical activity, throughout life.
    • Caloric restriction.
    • Semi-vegetarianism, food largely sourced from plants.
    • Moderate alcohol consumption (especially red wine).
    • Give meaning and purpose to life.
    • Reduced stress.
    • Engagement in spirituality or religion.
    • Family is at the centre of life.
    • Social commitment, integration in the community.