and triglyceride levels, all positively linked to obesity. Even 1 week of hypercaloric feeding may result in elevated fasting plasma insulin, glucose, and triglyceride levels and to exacerbated insulin response, without any weight gain. These findings suggest that the observed metabolic disturbances during excess caloric intake are not necessarily linked to obesity.
Key Point
Observed metabolic disturbances during excess caloric intake are not necessarily linked to obesity.
Epidemiological data suggest that intake of energy‐dense foods (i.e., more than 225–275 kcal/100 g of food), consumers’ exposure to large serving sizes, and overeating may contribute to obesity and, therefore, increase the risk for the development of chronic diseases. Overeating has also been associated with increased aging rate and decreased lifespan. According to the “rate‐of‐living/oxidative damage” theories, lifespan extension is linked to low energy metabolism, low reactive oxygen species (ROS) production rates, low molecular damage, and slow aging. Long‐term caloric restriction studies in humans show persistent metabolic slowing accompanied by reduced oxidative stress, evidence supporting the “rate‐of‐living/oxidative damage” theories of mammalian aging.
Saturated Fatty Acids
It is now generally accepted that the effects of SFAs on CVD depend mainly on what replaces them in the diet. For example, the substitution of omega‐3 polyunsaturated fatty acids (PUFAs) and monounsaturated fatty acids for SFAs might reduce CHD risk. On the other hand, replacing SFA with carbohydrates has mixed results over the CVD risk, while there is some evidence suggesting that whole grains but not refined carbohydrates reduce CVD risk.
Key Point
It is now generally accepted that the effects of SFA on CVD depend mainly on what replaces them in the diet.
In populations following Western dietary habits, it has been shown that when 5% of the energy derived from SFAs is replaced by PUFAs, LDL cholesterol concentrations decrease. In turn, this change can generate a decrease in CHD occurrence and deaths. Males from the Health Professionals Follow‐up Study and females from the Nurses' Health Study (NHS) were followed prospectively for 24–30 years; people with the highest consumption of PUFAs had 20% lower CHD risk compared to those who consumed a diet low in PUFAs. Notably, for every 5% decrease of energy coming from SFAs, the CHD risk decreased by 25% when an equal amount of energy was replaced by PUFAs. Similarly, combined scientific data from randomized controlled trials (RCTs) have demonstrated that individuals with increased PUFA intake, instead of SFAs, were 20% less likely to develop CHD, compared with those following a higher SFA diet. The protective effect against CHD incidence was 10% for every 5% of energy replacement by PUFAs, and the magnitude of this beneficial effect was contingent on the duration of the intervention.
Mixed results have been reported when total carbohydrates replace SFA, showing either no overall benefit, reduction, or even increased CVD risk. However, when separating whole grains from refined carbohydrates, isocaloric substitution of whole grains for SFA is associated with a decreased risk of CHD; CHD risk does not change in the case of isocaloric substitution of refined starches/added sugars for SFA.
Current guidelines recommend decreasing saturated fat intake to improve blood lipids and reduce cardiovascular risk. Dairy products have been thought to increase the risk of CVD, due to their high SFA, cholesterol, and calorie content. Indeed, most of the existing dietary guidelines for the prevention and management of cardiometabolic risk recommend low‐fat or nonfat dairy consumption. However, robust evidence from prospective studies shows no increase or even a small benefit in CVD risk from high dairy consumption (e.g., yogurt and cheese). The potential mechanisms of the attenuating effects of dairy foods remain to be fully elaborated but seem to involve food matrix effects on fat bioavailability, changes in the gut microbiome, and glucose, insulin, and other hormonal responses.
Key Point
Robust evidence from prospective studies shows no increase or even a small benefit in CVD risk from high dairy consumption.
Trans Fatty Acids
TFAs are present in foods such as meat and dairy products from ruminant animals (i.e., cattle, sheep, goats, and camels). However, more TFAs are generated during the manufacturing process of partially hydrogenated vegetable and marine oils, such as margarines, confectionary fats, and fat spreads. Foods that commonly contain margarine (such as deep‐fried foods, baked goods, and snacks) are therefore high in TFAs. Compared to animal fats, hydrogenated vegetable oils are more stable and less likely to become rancid during repeated deep‐frying processes and have greater stability at room temperature. Thus, they are widely used for commercial purposes.
However, TFA intake has been positively and robustly associated with increased risk of CHD and related mortality. The Zutphen Elderly Study showed a positive correlation between intake of TFAs and 10‐year risk for CHD. It was shown that for every 2% increase in TFA‐derived energy at baseline, there was 28% greater risk to develop CHD within the next decade. In the NHS, the 20‐year CHD risk for the women with high trans‐fat intake was associated with 1.3‐fold, i.e. 130% greater risk, compared to their counterparts with the lowest TFA intake, particularly the younger women.
The underlying mechanism by which TFAs increase CVD risk is probably related to changes in lipoprotein profile. Even moderate levels of TFA intake may lead to increased LDL concentrations, while high‐density lipoprotein (HDL) concentrations usually decrease. A meta‐analysis of RCTs exploring the impact of either naturally occurring or industrially produced TFAs on plasma LDL to HDL ratio revealed that, independently of their source, all TFAs can lead to an increase in the LDL to HDL ratio. However, others have challenged these findings; they suggested that the high variability in types of oils and interventions used in the various studies precludes drawing safe conclusions on the effect of specific types of TFAs on lipoproteins levels and CHD risk (i.e., naturally occurring or industrially produced TFAs). Indeed, a systematic review and meta‐analysis of prospective studies found that industrially produced but not naturally occurring TFAs are associated with increased risk of CHD.
Interestingly, growing evidence supports the notion that specific animal‐derived TFAs not only do not have detrimental health effects but may also be beneficial for human health. The naturally occurring trans‐palmitoleic acid, mainly found in whole‐fat dairy products, was associated with reduced CHD mortality, while no association was found with the industrially produced TFAs in a 10‐year study by Kleber and co‐workers. Finally, in a 2016 systematic review and meta‐analysis authorized by the WHO, it was found that the replacement of total or industrial TFAs with either monounsaturated fatty acids (MUFAs) or PUFAs results in improvements in the lipid and lipoprotein profiles, which further lead to the reduction of CVD risk.
Key Point
Industrially produced but not naturally occurring TFAs are associated with increased risk of CHD.
Another mechanism through which high TFA consumption can add to the CVD risk is by increasing inflammation and endothelial dysfunction. Data from the Nurses' Health Study I (NHS‐I) have shown that women who were free of CVD, cancer, and diabetes at baseline and who consumed a diet high in TFAs were more likely to have increased levels of inflammation and endothelial dysfunction. The positive relationship between TFA intake and systemic inflammation was also evident in an NHS‐II cohort; a modest mitigation of this association after controlling for serum lipid
