A pro-inflammatory diet increases the risk of dementia

A pro-inflammatory diet increases the risk of dementia

Professeur titulaire au Département de Médecine de l’Université de Montréal. Directeur du Centre ÉPIC de l’Institut de cardiologie de Montréal.23 December 2021

OVERVIEW

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

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

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

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

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

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

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

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

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

Lignans: Compounds of plant origin that promote good cardiovascular health

Lignans: Compounds of plant origin that promote good cardiovascular health

Cardiologue et Directeur de la prévention, Institut de Cardiologie de Montréal. Professeur titulaire de clinique, Faculté de médecine de l'Université de Montréal. / Cardiologist and Director of Prevention, Montreal Heart Institute. Clinical Professor, Faculty of Medicine, University of Montreal.14 October 2021

OVERVIEW

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

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

Figure 1. Structures of the main dietary lignans

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

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

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

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

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

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

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

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

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

Modulation of the gut microbiota by dietary interventions to prevent cardiometabolic diseases

Modulation of the gut microbiota by dietary interventions to prevent cardiometabolic diseases

Cardiologue et Directeur de la prévention, Institut de Cardiologie de Montréal. Professeur titulaire de clinique, Faculté de médecine de l'Université de Montréal. / Cardiologist and Director of Prevention, Montreal Heart Institute. Clinical Professor, Faculty of Medicine, University of Montreal.24 May 2021

OVERVIEW

  • In a study of 307 participants, the Mediterranean-style diet was associated with a composition of the gut microbiota conducive to good cardiometabolic health.
  • In another study, intermittent fasting altered the gut microbiota and prevented the development of hypertension in rats that spontaneously became hypertensive as they aged.
  • The metabolism of bile acids modulated by the microbiota has been identified as a regulator of blood pressure.
  • Dietary interventions aimed at modifying the gut microbiota could be a viable non-pharmacological approach to prevent and treat high blood pressure and other conditions.

Cardiometabolic diseases including type 2 diabetes and cardiovascular disease are on the rise in Canada and around the world. These diseases, which reduce the quality of life and life expectancy of those affected and generate significant costs for society, can be prevented by maintaining good lifestyle habits, including a healthy diet and regular exercise.

Recent studies have linked microbial metabolism and immune interactions in the gut and the risk of cardiometabolic disease (see our articles on the subject here, here and here). Two new studies show that the type of diet and the frequency of meals have effects on the risk of metabolic disease, which are in part due to alterations in the gut microbiota. The results of these new studies suggest that modulation of the gut microbiota by dietary interventions could be a new preventive and therapeutic approach.

US researchers analyzed the microbiome data of 307 male participants in the Health Professionals Follow-up Study as well as their eating habits and biomarkers of blood glucose regulation, lipid metabolism and inflammation. The Mediterranean-style diet (consisting mainly of vegetables, legumes, fruits, nuts, olive oil, and some wine and red meat) was associated with a composition of the gut microbiota conducive to good cardiometabolic health. The positive association between the Mediterranean-style diet and a lower risk of cardiometabolic disease was particularly strong among participants whose microbiota contained little Prevotella copri bacteria. Researchers do not yet understand why the Mediterranean diet is less effective in people whose microbiota contains the bacterium Prevotella copri, however, they make several hypotheses that will need to be verified in future studies. In any case, it can be envisaged that prevention approaches may one day be personalized according to the intestinal microbial profile of each person.

Benefits of intermittent fasting for hypertension
Intermittent fasting involves compressing the time during which one eats over a short period (6-8 h) and “fasting” the rest of the day (16-18 h). Intermittent fasting has positive effects on weight and body fat loss, chronic inflammation, metabolism, and cardiovascular health (see our articles on the subject here and here). The main metabolic benefits of intermittent fasting are reduced blood LDL cholesterol levels, increased insulin sensitivity and better blood glucose control in diabetics, reduced oxidative stress and inflammation. On the one hand, we know that an imbalance in the intestinal microbiota (intestinal dysbiosis) contributes to the development of hypertension. On the other hand, studies in recent years have shown that fasting and caloric restriction significantly reduce blood pressure, both in animal models and in hypertensive patients.

A recent study shows that the beneficial effects of intermittent fasting on blood pressure are attributable, at least in part, to the modulation of the gut microbiota. The researchers used an animal model commonly used in hypertension research: spontaneously hypertensive stroke-prone (SHRSP) rats, a unique genetic model of severe hypertension and stroke. Hypertensive SHRSP rats and normotensive Wistar-Kyoto (WKY) rats were subjected for 8 weeks to one or the other of the following diets: 1) ad libitum throughout the study (control groups) or 2) a diet alternating a day with food at will and a day without access to food (intermittent fasting). Hypertensive (SHRSP) and normotensive (WKY) rats in the control groups ingested the same amount of food. In contrast, the rats subjected to intermittent fasting ate more on days with food at will than those in the control groups, presumably to compensate for the fasting day. Despite this, the total amount of food ingested during the study was significantly lower in hypertensive (-27%) and normotensive (-35%) rats subjected to intermittent fasting, compared to animals in the respective control groups that had access to food at will. Despite a similar food intake, the hypertensive rats in the control group gained significantly less weight than the normotensive rats.

As expected, the blood pressure of hypertensive rats measured weekly was significantly higher than that of normotensive rats. In contrast, intermittent fasting significantly reduced blood pressure in hypertensive rats by an average of about 40 mmHg by the end of the study, compared to hypertensive rats who had access to food at will. This significant decrease brought the blood pressure of hypertensive rats to levels comparable to those of normotensive rats.

Role of the gut microbiota in the regulation of blood pressure
Animal models allow experiments on the role of the gut microbiota that could not be done in humans. In order to find out whether the gut microbiota plays a role in the effect of intermittent fasting, the researchers continued their studies by “transplanting” the microbiota from hypertensive and normotensive rats into “germ-free” rats, i.e. rats reproduced under special conditions in such a way that they do not contain any microorganisms.

Germ-free rats that received microbiota from hypertensive rats had significantly higher blood pressure than those that received microbiota from normotensive rats when subjected to the control diet (ad libitum). In contrast, intermittent fasting reduced the blood pressure of germ-free rats that received microbiota from hypertensive rats to levels comparable to those of rats that received microbiota from normotensive rats. These results demonstrate that the alterations in the microbiota of hypertensive rats caused by intermittent fasting are sufficient to cause a reduction in blood pressure. Analysis of the microbiota by whole-genome shotgun sequencing has enabled researchers to identify bile acid metabolism as a potential mediator of blood pressure regulation. Subsequent analyses revealed that the blood levels of 11 bile acids (out of 18) in hypertensive SHRSP rats were significantly lower than those in normotensive rats. In support of the hypothesis, the addition of cholic acid (a precursor of bile acids) in the food or the activation of the bile acid receptor (TGR5) significantly reduced the blood pressure (by 18 mmHg) of hypertensive rats.

In summary, the quality of food and frequency with which we eat has a significant impact on the microorganisms in our microbiota, cardiometabolic risk factors and, ultimately, our overall health. By changing the diet and the frequency of meals, it may be possible to significantly improve the condition of people with chronic diseases.

Control of inflammation through diet

Control of inflammation through diet

Cardiologue et Directeur de la prévention, Institut de Cardiologie de Montréal. Professeur titulaire de clinique, Faculté de médecine de l'Université de Montréal. / Cardiologist and Director of Prevention, Montreal Heart Institute. Clinical Professor, Faculty of Medicine, University of Montreal.23 November 2020

OVERVIEW

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Olive oil, the best source of fat for cooking

Olive oil, the best source of fat for cooking

Cardiologue et Directeur de la prévention, Institut de Cardiologie de Montréal. Professeur titulaire de clinique, Faculté de médecine de l'Université de Montréal. / Cardiologist and Director of Prevention, Montreal Heart Institute. Clinical Professor, Faculty of Medicine, University of Montreal.30 March 2020

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

Cardiologue et Directeur de la prévention, Institut de Cardiologie de Montréal. Professeur titulaire de clinique, Faculté de médecine de l'Université de Montréal. / Cardiologist and Director of Prevention, Montreal Heart Institute. Clinical Professor, Faculty of Medicine, University of Montreal.5 February 2020

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.