Early evidence on dietary fats and CVD was based on comparisons of incidence and mortality rates across geographical areas, and on knowledge of the effects of dietary fats on blood cholesterol levels. In the Seven Countries Study (>79), per capita intake of saturated fat, but not total fat, was strongly correlated with rates of CVD; although potentially confounded by other variables, this provided a strong incentive to understand the major geographical variation in CVD rates. In controlled feeding studies lasting several weeks, compared isocalorically to carbohydrate, saturated fat increased blood cholesterol concentrations, whereas PUFA reduced them (>80, >81). Thus, from the 1960s, dietary advice to reduce CVD emphasized replacing saturated fat with PUFAs, primarily N-6, and consumption of N-6 PUFA in the United States increased from approximately 3% to 7% of energy. Concurrently, age-adjusted coronary heart disease mortality decreased by about 75%, although lower rates of tobacco use and other prevention efforts (e.g., statins) contributed to this secular trend.
In subsequent epidemiologic studies, blood lipid subfractions predicted CVD better than did total cholesterol; higher amounts of LDL cholesterol and triglycerides are associated with higher risk, whereas higher amounts of HDL cholesterol predict lower risk (>82). In further controlled feeding studies, replacement of saturated fat with carbohydrates reduced both LDL cholesterol and HDL cholesterol and increased blood concentrations of triglyceride during fasting, suggesting little or potentially adverse effects on risk of CVD. Replacement of monounsaturated or polyunsaturated fat with carbohydrate increased LDL cholesterol and had minimal effects on HDL cholesterol or triglycerides.
Consistent with the controlled feeding studies of blood lipids, in several randomized trials with CVD as the outcome, replacement of saturated fat with PUFA reduced the risk of CVD, whereas replacement with carbohydrate did not (>83); however, these studies were small, short-term, and had other limitations (e.g., a lack of emphasis on carbohydrate quality). Long-term prospective cohort studies are also consistent with these findings: When compared isocalorically with saturated fat, N-6 PUFAs—but not typical carbohydrates in Western diets—are associated with lower risk of CVD (>84–>86). Controlled for other types of fat, MUFAs are also inversely associated with risk. This inverse association with PUFA is linear up to about 8% of energy, beyond which data are sparse. These epidemiologic studies also highlight the importance of carbohydrate quality; relative to saturated fat, whole grains are associated with lower CVD risk (>87).
By the 1990s, the distinction between N-6 and N-3 PUFAs and between cis and trans isomers gained widespread recognition. In animals, N-3 fatty acids protect against cardiac arrhythmias, and in epidemiologic studies, intakes of N-3 fatty acids [DHA or eicosapentaenoic acid (EPA) from fish and ALA from plant sources] are inversely but nonlinearly associated with risk of sudden cardiac death (>88). Specifically, risk decreases with intakes up to about 250 mg/day (equivalent to one or two servings of fish per week) but then plateaus. The inconsistent effects of supplements seen in these RCTs may relate to the variability in intakes within and among populations (intakes among some individuals in the United States and mean intakes in many countries remain very low) (>89). At high dosage, fish oil supplements may reduce the risk of cardiovascular events such as heart attack and stroke among people with hypertriglyceridemia, according to preliminary data from a large trial (>90)—a possibility that warrants further study.
The main N-6 PUFA in diets, linoleic acid, can be elongated and desaturated to form eicosanoids that are prothrombotic and proinflammatory. In addition, linoleic acid may competitively inhibit biosynthetic pathways shared by the N-3 fatty acid ALA in the formation of antithrombotic and anti-inflammatory eicosanoids. For these reasons, some have concluded that higher N-6 fatty acid intake should be minimized to prevent CVD and other diseases associated with chronic inflammation. However, this reasoning disregards evidence that N-6 PUFA intermediates in these pathways, such as arachidonic acid, are highly regulated (>91). Although very high intakes of N-6 PUFA increase inflammatory measures in some animal models, this effect has not been convincingly demonstrated in humans (>92); higher intake of linoleic acid in humans may actually have anti-inflammatory effects (>93). Moreover, the ratio of N-6 to N-3 fatty acids has not been associated with risk of CVD, consistent with both being beneficial (>94). Nonetheless, special effects in subgroups or at very low intakes of carbohydrate cannot be ruled out.
The process of partial hydrogenation, which creates trans isomers from the natural cis double bonds of fatty acids, was widely used to create margarine and vegetable shortening with favorable commercial properties (solidity at room temperature, long shelf life). This industrial process altered the structure and function of linoleic acid and ALA, the dominant fatty acids in many widely used oils, resulting in major health impacts. Trans fat has uniquely adverse effects on LDL, LDL particle size, HDL, triglycerides, and inflammatory factors (>95). In multiple large-cohort studies, intake of trans fat is directly associated with risk of coronary heart disease and other chronic illnesses. Through regulations, education, and food labeling, trans fat was largely eliminated from the food supply in the United States and some European countries. However, intake remains high in some parts of the world.
Source : https://science.sciencemag.org/content/362/6416/764.full