INTRODUCTION — Historically, a chief health concern about dietary fats has been their role in promoting or protecting against coronary heart disease; other concerns relate to their possible roles in the genesis of diabetes, stroke, obesity and cancers. Following decades of research, the relationship between fat intake and these health outcomes is becoming clearer. While historical recommendations from several authoritative United States organizations over the past several decades emphasized decreasing the total amount of fat in the diet, the overall body of research indicates that the type of fat is far more important than the proportion of calories from total fat. Consistent with this, the 2015 Dietary Guidelines Advisory Committee (DGAC) recommended no upper limit on the percentage of calories from total fat, and the 2020 DGAC did not re-review this evidence [1,2].
Issues regarding dietary fat are reviewed here. The management of patients with hypercholesterolemia and the role of diet and dietary supplements in lipid lowering are discussed separately. (See "Low-density lipoprotein cholesterol-lowering therapy in the primary prevention of cardiovascular disease" and "Lipid management with diet or dietary supplements".)
RECOMMENDATIONS FOR PATIENTS — For patients who do not require special diets for existing diseases (eg, chronic kidney disease, celiac disease, eating disorder), it is reasonable to suggest that patients:
●Do not focus on trying to restrict total fat intake; instead, increase consumption of minimally processed, bioactive-rich foods like fruits, nuts, seeds, vegetables, legumes, whole-grain products, plant oils, yogurt, and seafood, which are linked to lower risk of cardiovascular diseases, diabetes, and obesity. Reduce consumption of processed meats and carbohydrate-rich foods high in refined starch, added sugars, trans fat, or sodium. Cheese, milk, eggs, poultry, and unprocessed red meats may be added in moderation.
●Do not assume that low-fat or "fat-free" varieties of packaged and processed foods (eg, snack foods, salad dressings) are more healthful or better for weight control [3]. These foods are often rich in refined starches and added sugars, which have been associated with higher triglyceride-rich lipoproteins and lower high-density lipoprotein (HDL) cholesterol levels [4], a possible increase in the incidence of type 2 diabetes [5,6] and obesity [7], and failure to gain the benefits of more healthful alternatives.
●Reduce the intake of industrially produced trans fatty acids by avoiding foods containing partially hydrogenated vegetable oils (eg, vanaspati or stick margarine, commercially baked goods, deep-fried fast foods, and street vendor foods). In the United States, the US Food and Drug Administration (FDA) has determined that partially hydrogenated vegetable oils are no longer "generally regarded as safe" (GRAS), which has largely removed such industrial trans fats from the United States food supply [8].
●When fats are needed for cooking, spreads, sauces, dressings, and other uses, use plant oils from fruits, seeds, and nuts with high amounts of monounsaturated and/or polyunsaturated fatty acids, especially n-3 polyunsaturated fats, including canola oil, soybean oil, and extra-virgin olive oil (figure 1).
●Choose foods rich in healthy fats including nuts, seeds, avocadoes, and fish.
These suggestions are generally consistent with the 2020 Dietary Guidelines for Americans [1]. (See 'Dietary fat advice' below.)
As discussed below, health effects of dairy fats remain uncertain and controversial. Most guidelines continue to recommend low-fat dairy products.
TOTAL FAT INTAKE — There are several reasons to be circumspect regarding recommendations to reduce total fat intake to below 35 percent of energy (recommended by the 2002 Dietary Reference Intakes [DRI] and not yet updated to incorporate newer evidence). Since the total fat DRI was set in 2002, multiple cohort studies and randomized clinical trials have shown that lowering total fat intake has no meaningful effects on heart disease, stroke, cancers, diabetes, or long-term weight control [9]. This is likely because total dietary fat includes different fatty acids and food sources with divergent effects on health; and because a reduction in dietary fat is almost always accompanied by an increase in carbohydrates, in particular refined starches and sugars. An emphasis on total fat intake has thus tended to obscure our appreciation of disease-protecting dietary patterns which are based fundamentally on types of foods, rather than macronutrient targets (such as the percentage of energy from total fat) [2].
Other issues with regard to the recommendation for a low-fat diet include:
●The role of dietary fat in the etiology of obesity remains controversial. Some scientists and organizations continue to recommend low-fat diets. Others recommend only calorie counting without regard to specific macronutrient targets, and still others recommend high-fat, low-carbohydrate diets. (See "Obesity in adults: Dietary therapy".)
●Compared with making recommendations about specific foods, it is difficult to communicate to patients how to achieve a target level of total fat intake.
●The message to reduce dietary fat has been translated by food manufacturers and consumers into a potentially harmful set of food choices, particularly ultra-processed foods rich in starch and sugar, which appear to have contributed to the obesity and type 2 diabetes epidemics.
Effects of total dietary fat intake — The evidence is weak that a high intake of total fat per se is harmful in terms of heart disease, stroke, cancer, or obesity.
Heart disease — Populations with a higher total fat intake do not always have more heart disease [10,11]. In the Seven Countries Study, for example, the locations with the lowest incidence of coronary heart disease were Crete and Japan [10]. However, the Japanese had a very low fat intake, while individuals in Crete typically had a high total fat intake, chiefly composed of monounsaturated fats from vegetable sources (olive oil).
Ecologic comparisons across populations can be confounded by other factors. However, even cohort studies of individuals within a population have not produced compelling evidence that total fat intake is associated with the incidence of coronary heart disease. As an example, in an analysis from the Nurses' Health Study involving 20-year follow-up of 80,000 women, the multivariate adjusted relative risk (RR) of coronary heart disease for the highest quintile of dietary fat compared with the lowest was 0.92 (95% CI 0.77-1.09) [12]. A meta-analysis of cohort studies, including the Nurses' Health Study, revealed no association of total fat intake with either coronary events or death [13]. In the international Prospective Urban Rural Epidemiology (PURE) cohort study, 135,335 individuals from 18 countries were followed for total mortality and major cardiovascular events [11]. Intake of total fat was not significantly associated with risk of myocardial infarction or cardiovascular disease (CVD) mortality.
Only a small number of randomized trials have examined the effect of changing diet upon cardiovascular end points, and few have achieved substantial differences in total fat intake between the intervention and control diets [14-17]. The largest such study, the Women's Health Initiative, randomly assigned 48,835 women (97 percent with no history of CVD) to an intensive behavior-modification group, with a goal of reducing total fat intake to 20 percent of calories and increasing daily intake of vegetables and grains, or to a control group who received dietary education materials; mean follow-up was 8.1 years [15]. After six years, women in the intervention group had decreased total fat intake compared with the control group (28.8 versus 37.0 percent of calories from fat), but the intervention had no effect on overall coronary heart disease (hazard ratio [HR] 0.94, 95% CI 0.86-1.02) or stroke (HR 1.02, CI 0.90-1.17). Although the intervention group reduced the potentially harmful saturated and trans fats, they also reduced the potentially beneficial monounsaturated and polyunsaturated fats [16] while increasing refined carbohydrates. (See 'Quality of fat' below.)
In prespecified subgroups analyses of this trial, the low-fat intervention significantly (p<0.01) increased the risk of recurrent coronary heart disease among women with prevalent CVD at baseline.
Cancer — The relationship between fat intake and the development of cancer is even less well-documented than that of coronary heart disease. Some cross-cultural studies have suggested a role for high total fat intake in the genesis of breast, colon, and prostate cancers, but these studies, like those of heart disease, could be confounded by other factors.
●Case-control studies of diet and breast cancer have suggested a modest role for total fat intake. In one summary of results from 12 case-control studies, the relative risk of breast cancer was estimated to be 1.35 for each 100 g increment in daily intake of fat [18]. By contrast, cohort studies, which do not have the inherent recall bias of case-control studies, have generally not found this association. In a pooled analysis of seven cohort studies, for example, each 25 g increment of fat intake, adjusted for energy intake, was associated with a relative risk of breast cancer of only 1.05 (95 percent confidence interval 0.94 to 1.11) [19]. Furthermore, in an analysis of the Nurses' Health Study, a prospective cohort study of 88,795 women, there was no evidence that either lower total fat intake or lower intake of specific types of fat decreased the risk of breast cancer [20].
●Associations between fat intake and colon cancer may be explained by red meat consumption rather than total fat intake [21].
●Systematic reviews from the WCRF/AICR continuous update project have concluded that there is no probable or convincing evidence that total dietary fat influences the risk of any cancers [22].
●Consistent with these observational studies, the Women's Health Initiative randomized clinical trial described above found that, at a mean follow-up of 8.1 years, the intervention to reduce total fat intake did not significantly affect the risk of colorectal cancer (HR 1.08, 95% CI 0.90-1.29) or breast cancer (HR 0.91, CI 0.83-1.01) [23,24].
Obesity — The prevalence of obesity in the United States has been rising for decades [25-27], prompting researchers to examine the role of dietary constituents in promoting an increase in body fat.
The comparative roles of different diet compositions, including low-fat diets, in reducing weight are discussed in detail separately. (See "Obesity in adults: Dietary therapy".)
Type 2 diabetes — In a meta-analysis of eight observational cohort studies, total dietary fat consumption was not associated with incidence of diabetes [28]. Further, in the Women's Health Initiative randomized trial, significant lowering of total fat intake over mean 8.1 years of follow-up had no significant effect on incidence of diabetes or on insulin resistance [29].
Total mortality — In the large international PURE cohort study including a mix of high-, middle-, and low-income countries, lower intakes of total fat were associated with significantly higher risk of death from all causes [11]. While the results may be confounded from poorer individuals consuming more starchy staples and having less access to (often more expensive) animal source foods, the findings provide little support for health benefits of lowering total fat consumption.
QUALITY OF FAT — The quality of fat consumed and its food sources appear to be considerably more important for health than total fat intake (table 1) [13]. In general, industrial trans fats should be avoided. The Dietary Guidelines for Americans have concluded that substituting polyunsaturated for saturated fats appears to lower cardiovascular risk [30], whereas substituting carbohydrates for saturated fat does not reduce risk (and may cause excess weight gain). (See 'Polyunsaturated fatty acids' below.)
Trans fatty acids — Low levels of trans fatty acids occur naturally in some foods, especially dairy and meats from ruminants (cows, sheep, goats). However, much higher levels of trans fatty acid consumption can occur as a result of the industrial partial hydrogenation of unsaturated fatty acids. Trans fatty acids from this source appear to confer harmful cardiovascular effects [31-37].
Starting in 2006, the US Food and Drug Administration (FDA) required that Nutrition Facts labels include trans fat content. Several areas in the United States and Europe have passed legislation to restrict trans fats from foods served commercially [38,39]. In 2018, the FDA implemented its 2015 ruling that partially hydrogenated vegetable oils are no longer "generally regarded as safe" (GRAS), effectively removing industrial trans fatty acids from the United States' food supply [8].
Nonetheless, industrial trans fatty acids remain present in many nations. Globally, today's margarines, which are generally softer than the older varieties, contain less trans fatty acids than previously [40]. However, trans fatty acids are still a component of many international commercial baked goods, such as cookies and cakes, and deep-fried foods. A clue to their presence is the words "partially hydrogenated" on the list of package ingredients. Partially hydrogenated oils are also commonly used in low- and middle-income countries by street vendors and restaurants for frying and cooking.
Trans fatty acids raise blood low-density lipoprotein (LDL) and lower high-density lipoprotein (HDL) cholesterol concentrations [32]. In a meta-analyses of randomized controlled feeding studies, each 1 percent energy consumption of trans fatty acids in place of saturated fats, monounsaturated fats, or polyunsaturated fats, respectively, increased the total cholesterol to HDL cholesterol ratio by 0.31, 0.54 and 0.67; increased the apolipoprotein (Apo)-B/ApoAI ratio by 0.007, 0.010 and 0.011; and increased lipoprotein (Lp)(a) by 3.76, 1.39 and 1.11 mg/L (p<0.05 for each) [41].
By comparison, consumption of saturated fats, as compared with carbohydrate, also raises LDL cholesterol concentrations but concurrently lowers levels of triglyceride-rich lipoproteins and raises HDL cholesterol, with no net change in the total cholesterol to HDL ratio (see 'Saturated fatty acids' below). Thus, effects of saturated fats on the lipid profile are far less adverse than those of trans fatty acids.
Trans fatty acids may also interfere with the desaturation and elongation of n-3 (omega-3) fatty acids. These are important for the prevention of heart disease and complications of pregnancy. (See 'Heart disease' below.)
Several observational studies have linked the consumption of trans fatty acids, or foods that contain them, with adverse cardiovascular outcomes [31-36,42,43]. In an analysis from the Nurses' Health Study, for each increase of 2 percent of energy from trans fat, the relative risk for incident coronary heart disease was 1.93 (95% CI 1.43-2.61) [31]. Calculations suggest that replacement of trans fatty acids with other sources of fat, even saturated fatty acids, can reduce coronary risk [41].
Trans fat intake does not appear associated with diabetes risk. Based on a meta-analysis of seven cohorts, estimated trans fat consumption from dietary questionnaires was not significantly associated with incident type 2 diabetes [28]; and, based on individual-level analyses from an international consortium of 18 prospective studies with measured blood biomarkers, trans fatty acid blood levels were not associated with higher incidence of diabetes [44].
In contrast to the trans fatty acids discussed above, trans-palmitoleic acid is a trans fatty acid derived from naturally occurring dairy and other ruminant trans fats. Biomarkers of trans-palmitoleic acid intake are not associated with higher cardiovascular risk [32] and indeed have been associated with lower risk of diabetes in several cohort studies, perhaps conferring benefit by decreasing insulin resistance [45]. In a pooled de novo analysis among 63,682 participants from 16 prospective cohorts across 12 countries, higher blood biomarker levels of trans-palmitoleic acid were associated with lower incidence of type 2 diabetes, with 18 percent lower risk across the interquintile range [46]. (See "Type 2 diabetes mellitus: Prevalence and risk factors", section on 'Dairy products'.)
More research is needed to determine the causality and mechanisms underlying a possible metabolic benefit of trans-palmitoleic acid or its major food sources. The evidence is strong to reduce consumption of trans fatty acids from partially hydrogenated vegetable oils and other industrial sources, given their adverse effects on cardiovascular risk factors discussed above.
Saturated fatty acids — While recommendations on saturated fat have conventionally grouped all saturated fatty acids together, increasing evidence indicates that different saturated fatty acids, and different food sources of saturated fat, have divergent effects on cardiovascular and metabolic health [47]. For example, saturated fatty acids with carbon chain lengths of 14 (myristic) and 16 (palmitic), chiefly found in dairy products and red meats, appear most potent in increasing both LDL and HDL cholesterol (figure 2) [48] and decreasing triglyceride-rich lipoproteins. Stearic acid (18 carbons), another component of beef and the chief fatty acid of cocoa butter, has far smaller effects on LDL and HDL cholesterol. Combining these effects on different lipid fractions, compared with isocaloric consumption of total carbohydrate, the consumption of myristic and palmitic acid have relatively little effect on the ratio of total cholesterol to HDL cholesterol, while stearic acid and especially lauric acid (12 carbons) significantly lower this ratio (figure 3).
Studies have shown a continuous, graded relationship between the total serum cholesterol concentration and coronary heart disease events and mortality (figure 4) [49,50]. However, concentrations of triglycerides and HDL cholesterol also independently predict risk. Thus, more discriminative predictors of risk appear to be ratios such as the ratio of total to HDL cholesterol, the ratio of non-HDL to HDL cholesterol, or the ratio of ApoB to ApoA1 particles. Consistent with a neutral effect of the most common dietary saturated fats, palmitic and myristic, on these ratios, systematic reviews and meta-analyses of prospective observational studies found no association between the overall intake of total saturated fat and risk for coronary heart disease [37,51] or onset of type 2 diabetes [28].
By contrast, higher consumption of unsaturated fats improves blood cholesterol and lipoprotein ratios, whether in comparison with total carbohydrate or total saturated fat. Consistent with benefits of unsaturated fats, some systematic reviews and meta-analyses have found that replacing saturated fats with polyunsaturated fats (instead of carbohydrates) appears to decrease the risk of coronary heart disease events [52,53]. This is consistent with the conclusions of the 2020 Dietary Guidelines Advisory Committee (DGAC) that there is strong evidence that replacing saturated fats with polyunsaturated fats reduces the risk of coronary heart disease events and cardiovascular disease (CVD) mortality, there is limited evidence available on whether replacing saturated fats with monounsaturated fats improves CVD endpoints, and there is strong evidence that replacing saturated fat with carbohydrate does not reduce risk [1,54].
Thus, a focus on increasing intake of unsaturated fats, in particular polyunsaturated fats, is reasonable. The relative intake of saturated fat, in relation to unsaturated fats, may be more important than its absolute intake. In a randomized controlled feeding study, diets varying widely in saturated fat content (from 7 to 21 percent of energy) had no effect on LDL cholesterol concentrations when they were accompanied by similar proportional changes in unsaturated fats [55].
Very low intakes of saturated fat, such as levels below 7 percent of total calories such as seen in some Asian countries, have been linked to higher risk of stroke, especially hemorrhagic stroke, in individual cohort studies as well as the large multi-country PURE cohort [11]. Specifically, across quintiles, higher intake of saturated fat was associated with lower risk of total mortality (cross-quintile hazard ratio [HR] 0.86, 95% CI 0.76-0.99) and stroke (HR 0.79, 0.64–0.98). While causality of these associations have not been established, hypothesized mechanisms include increased cerebral vascular fragility from low intakes of saturated fat and/or animal protein.
Less is known about health effects of other saturated fatty acids. Medium-chain triglycerides (including saturated fats with carbon lengths at or below 12 carbons) have been thought to be metabolically protective, while very long-chain saturated fats (lengths of 20, 22, or 24 carbons) have been linked to lower risk of coronary heart disease and heart failure [56,57].
Food sources of saturated fat exhibit even more divergent associations with cardiovascular and metabolic risk than individual saturated fatty acids [47]. In particular, higher intakes of processed meats, but less so unprocessed red meats and not dairy fat or plant sources of saturated fats, are consistently linked to higher cardiovascular risk [58]. Higher intakes of processed meats, and to a lesser extent unprocessed red meats, are also linked to higher risk of type 2 diabetes [58]. Intake of dairy foods, especially yogurt and cheese, are linked to lower risk of type 2 diabetes. The mechanisms for the latter protective associations have not been confirmed but may include benefits of medium-chain triglycerides, vitamin K2, milk fat globule membrane, and several other compounds in dairy fat [59]. Relatively little is known about long-term health effects of tropical fruit oils, such as palm oil and coconut oil, which are rich in different saturated fats.
In sum, the divergent associations of different individual saturated fatty acids with blood lipids and clinical endpoints, and the divergent associations of different major food sources with clinical endpoints, have called into question the wisdom of maintaining a dietary recommendation that limits total saturated fat intake from all sources, as compared with food-specific recommendations [47,60,61]. Nonetheless, this remains controversial, and the 2018 draft World Health Organization (WHO) report on fatty acids maintains a recommendation to keep total saturated fat consumption below 10 percent of total calories. The 2020 DGAC report, while maintaining this general recommendation, adds that “the health effects of dietary saturated fat—or any other nutrient—depends not only on the total amount consumed, but also the specific type of saturated fatty acids inherent within the food matrix, sources and degree of processing, and the overall dietary pattern” [1]. Consistent with this, the 2020 DGAC partly translates the nutrient guidance to food-based guidance, “substituting some animal-source foods, especially processed meats and certain dairy products, with sources of polyunsaturated fats such as seafood, seeds, nuts, legumes, and appropriate vegetable oils,” rather than focusing on avoiding all saturated fat.
Monounsaturated fatty acids — In contrast to the diversity of individual saturated fatty acids, nearly all (90-plus percent) monounsaturated fat in foods is oleic acid, an 18-carbon fatty acid with a single double bond. Food sources of oleic acid (and therefore monounsaturated fatty acids) remain diverse, however, with much coming from red meats and dairy fats (each containing about equal amounts of saturated fat and monounsaturated fat) and a smaller amount coming from plant oils like nuts, avocadoes, and olive oil. Consumption of olive oil is high in Mediterranean countries such as Spain and Italy.
There is no consensus on recommendations for the consumption of monounsaturated fatty acids in the diet [62]. Meta-analyses of prospective observational studies and randomized trials found no association between intake of monounsaturated fat and risk for coronary heart disease [37,41]. A 2014 meta-analysis identified a protective association of monounsaturated fat intake in relation to coronary heart disease, but this association was limited to studies of olive oil, rather than studies of combined, animal, or other sources of monounsaturated fat [63].
Based on observational data and biologic plausibility for cardiovascular risk, some authors recommend an increase in monounsaturated fatty acids when saturated fatty acids are decreased, leading to no net decrease in total fat. Plant sources of monounsaturated fats include olive oil, canola oil, tree nuts, and avocadoes.
Replacing saturated fats with monounsaturated fats may decrease LDL cholesterol and triglycerides as well as maintain HDL cholesterol [64-66]. Monounsaturated fatty acids can also decrease the oxidation of LDL cholesterol, a key step in atherosclerosis [67]. The in vivo implications of these findings are not yet clear, in part because much of the monounsaturated fats in the United States diet have come from animal rather than vegetable sources, and many studies have not been able to distinguish the two sources. Thus, uncertainty remains on recommendations for the total consumption of monounsaturated fatty acids in the diet [62]. (See "Lipoprotein classification, metabolism, and role in atherosclerosis".)
A 2016 systematic review and meta-analysis including 102 randomized controlled feeding trials found that replacing carbohydrates with either monounsaturated fat or polyunsaturated fat improved several markers of glycemia including HbA1c [68].
In cross-cultural studies, Mediterranean populations that consume high amounts of monounsaturated fats from extra-virgin olive and nuts appear to be protected against heart disease [10]. A partially randomized trial evaluating this hypothesis demonstrated that extra virgin olive oil and mixed nuts, in combination with a traditional Mediterranean-type diet, reduced the risk of a composite outcome of heart attack, stroke, and death by about 30 percent (from approximately 11 to 8 events per 1000 person-years) [69]. In patients with type 2 diabetes mellitus, change from a polyunsaturated to monounsaturated diet reduces insulin resistance and restores endothelium-dependent vasodilatation, providing a possible mechanism by which a "Mediterranean diet" reduces the risk of atherosclerotic disease [70,71]. A similar benefit of a Mediterranean diet on endothelial function has been seen in hypercholesterolemic patients and in patients with the metabolic syndrome [72,73].
In sum, the evidence supports consuming plant foods rich in monounsaturated fat, in particular extra virgin olive oil and tree nuts, rather than trying to increase monounsaturated fats from all sources.
Polyunsaturated fatty acids — Polyunsaturated fatty acids can be categorized into two classes, the n-6 family of polyunsaturated fatty acids (eg, linoleic acid, arachidonic acid) and the n-3 family (eg, alpha-linolenic acid, eicosapentaenoic acid [EPA], docosahexaenoic acid [DHA]). The 18-carbon n-6 (linoleic) and n-3 (alpha-linolenic) fatty acids are essential nutrients, that is, they cannot be synthesized by humans, and their absence in the diet causes clinical deficiency. Thus, in contrast to saturated and monounsaturated fats, for which blood and tissue levels largely represent de novo synthesis in the liver from either dietary starch or sugars, blood and tissue levels of the major n-6 and n-3 fatty acids reflect dietary consumption.
Like monounsaturated fats, there is relatively little diversity in types of dietary n-6 fatty acids, which are predominantly (>90 percent) linoleic acid with small additional amounts of dietary arachidonic acid. Dietary n-3 fatty acids are either plant-derived (alpha linolenic acid, eg, from walnuts, canola, soybean) or fish/shellfish-derived (in particular EPA and DHA, present in all fish and shellfish but especially oily fish).
n-6 and n-3 fatty acids have been extensively studied in relation to cardiovascular, metabolic, and cancer risk factors and outcomes.
Heart disease — Intake of both n-6 and n-3 polyunsaturated fatty acids has been associated with decreased risk of coronary heart disease.
n-6 fatty acids — Based on randomized controlled feeding studies, it is well established that n-6 fatty acids from plant oils (eg, soybean, safflower, sunflower, and corn oils) improve lipid and lipoprotein profiles, lowering serum LDL cholesterol, ApoB levels, and triglycerides (very low-density lipoprotein [VLDL] cholesterol) while also increasing HDL cholesterol and ApoA1 levels, leading to a significant overall reduction in the ratio of total to HDL cholesterol and ratio of ApoB to ApoA1 [66]. Intake of n-6 fatty acids also improves long-term glycemic control, insulin resistance, and insulin production (see 'Diabetes mellitus' below). Some controlled trials have seen possible other benefits of n-6-rich plant oils, such as reduced liver fat accumulation and postprandial triglycerides [74,75].
Despite theorized proinflammatory effects of n-6 fatty acids, such effects are not seen in human trials [74,76,77].
Consistent with the beneficial effect on lipids and glycemia, meta-analyses of both estimated dietary consumption or objective measured blood biomarkers of total n-6 fatty acids and linoleic acid have been associated with lower risk of coronary heart disease. For example, in individual-level pooled analyses from 30 international prospective studies including nearly 70,000 participants, higher blood biomarker levels of linoleic acid were associated with lower risks of total CVD, cardiovascular mortality, and ischemic stroke, with hazard ratios per interquintile range of 0.93 (95% CI, 0.88-0.99), 0.78 (0.70-0.85), and 0.88 (0.79-0.98), respectively, and nonsignificantly with lower coronary heart disease risk (0.94; 95% CI 0.88-1.00). Blood biomarker levels of arachidonic acid were not associated with higher risk of cardiovascular outcomes, but rather with lower risk of total CVD across quintiles (0.92; 95% CI 0.86-0.99). Meta-analyses of mostly older, methodologically limited controlled trials demonstrate that replacing butter and other animal fats with n-6-rich oils (predominantly soybean oil) lowers the incidence of coronary heart disease. Notably, benefits for coronary heart disease in observational cohort studies are seen whether linoleic acid is consumed in place of total saturated fat or total carbohydrate [78].
Studies evaluating the ratio of n-6 to n-3 fatty acids in the diet or blood sometimes show that higher ratios are linked to worse health outcomes. However, such associations in humans are driven by differences in levels of n-3 fatty acids rather than differences in levels of n-6 fatty acids [79].
Based on the lipid and other physiologic benefits, meta-analyses of observational cohort studies, and older clinical trials, the US Dietary Guidelines and many other guidelines recommend diets rich in n-6 fatty acids [80].
n-3 fatty acids — The n-3 family of polyunsaturated fatty acids includes EPA and DHA, which are found in fish oil, especially cold-water oily fish such as salmon, anchovies, mackerel, herring, sardines, and tuna. The third member of the family is alpha-linolenic acid, which is found in the oil of plants such as walnuts, soybeans, and canola.
Supplement or prescription n-3 fatty acids, including their effects on cardiovascular risk factors, are discussed in detail elsewhere. (See "Fish oil: Physiologic effects and administration".)
The evidence for cardiovascular benefits of plant-derived alpha-linolenic acid remains uncertain. A meta-analysis of 27 observational studies demonstrated that top versus bottom tertile of dietary intake of alpha-linolenic acid was associated with a borderline significant 10 percent lower risk of CVD (13 studies, pooled relative risk [RR] 0.90, 95% CI 0.81-0.99), with a similar but not statistically significant inverse association for biomarker studies of alpha-linolenic acid [81]. In general, Americans tend to consume relatively low amounts of alpha-linolenic acid, which is found in canola oil and some nuts and seeds (eg, flaxseed) [82].
Stroke — Due to conflicting results of studies of n-6 and n-3 polyunsaturated fats and risk of stroke, no firm recommendations are yet warranted regarding the effect of polyunsaturated fat intake on stroke risk.
●Consumption of polyunsaturated fats (combined n-3 and n-6 fatty acids) in the Framingham study was not associated with risk of stroke, whereas intakes of both saturated and monounsaturated fats were associated with lower risk of ischemic stroke [83].
●By contrast, a prospective study of 43,732 men participating in the Health Professionals Follow-up Study found no association between stroke and the intake of saturated fat, monounsaturated fat, polyunsaturated fat, trans unsaturated fat, or dietary cholesterol [84]. Intake of n-3 and n-6 polyunsaturated fatty acids were also not associated with ischemic or hemorrhagic stroke.
●In separate reports from the Nurses' Health (women) and Health Professionals (men) studies, participants with higher intake of fish and n-3 fatty acids had a reduced risk of ischemic stroke [85,86]. In the men, eating fish once per month or more was associated with a reduced risk of ischemic stroke compared with fish consumption less than once per month (RR 0.57, 95% CI 0.35-0.95) [86]. In the women, the effect was strongest among those who did not take aspirin regularly [85]. A meta-analysis that included these studies also found a reduced risk of stroke with increased fish consumption [87], as did a subsequent observational study in 4775 older adults [88]. It is a challenge to put these findings in context with the null findings among men for all types of fat discussed above [84]. It is possible that fish intake may provide benefits by some other mechanism than n-3 fatty acids or may be a marker for other healthy behaviors that reduce the risk of stroke.
Diabetes mellitus — Data are conflicting on the relationship between polyunsaturated fats and the development of diabetes. One cohort study of 11-year follow-up among 36,000 women showed inverse relations with incident type 2 diabetes for intake of plant fat and substitution of polyunsaturated fatty acids for saturated fatty acids and dietary cholesterol [89]. Some additional studies have also suggested a protective role for polyunsaturated fatty acids and a harmful role for trans fats, though other studies have not [90].
In a systematic review and meta-analysis of 102 randomized controlled feeding trials, higher intakes of monounsaturated fat and polyunsaturated fat improved several markers of glycemia [68]. Specifically, consuming polyunsaturated fat in place of saturated fat reduced fasting glucose, HbA1c, and insulin resistance; and consuming polyunsaturated fat in place of carbohydrates, saturated fat, or monounsaturated fat also improved insulin secretion capacity. Replacing saturated fat with carbohydrates had no significant effect on fasting glucose, HAbA1c, or insulin resistance. These findings support a potential beneficial role of monounsaturated fatty acids and especially polyunsaturated fatty acids for glycemic control.
In a meta-analysis of observational cohort studies, dietary polyunsaturated fats were not associated with incidence of type 2 diabetes when evaluated as a linear-dose response, but in nonlinear analysis, protective associations were seen for dietary vegetable fats and polyunsaturated fats up to modest levels of intake [28]. In pooled analysis across 20 cohorts from 10 nations, blood biomarker levels of linoleic acid were inversely associated with incident diabetes, with 35 percent lower risk per interquintile range (RR 0.65, 95% CI 0.60-0.72). Biomarker levels of arachidonic acid were not significantly associated with type 2 diabetes risk overall (RR per interquintile range 0.96, 95% CI 0.88-1.05) [91].
Other diseases — Dietary fat intake may affect the risk of Alzheimer disease. Studies have suggested that intake of saturated fats and trans fats may increase the risk of Alzheimer disease and cognitive decline, while intake of monounsaturated and polyunsaturated fats may decrease this risk [92,93].
Dietary cholesterol — Dietary cholesterol raises the total serum cholesterol but is a less important contributor than saturated fat [94,95]. Eggs are a chief source of dietary cholesterol, but the association between regular egg consumption and risk of coronary heart disease and stroke is uncertain. As an example, in a 2013 meta-analysis of eight prospective cohort studies (more than 474,000 participants), there was no association between egg consumption and risk for coronary heart disease or stroke (RR 0.99 and 0.91 for each additional daily egg, 95% CI 0.85 to 1.15 and 0.81 to 1.02, respectively) [96].
For most individuals, only a minor emphasis on reducing dietary cholesterol alone is needed since it is a less important contributor to serum cholesterol and clinical endpoints than is saturated or trans fat [2,97]. However, some patients who either consume very large amounts of dietary cholesterol or whose serum LDL cholesterol response to moderate cholesterol intake is unfavorable may benefit from reduction in cholesterol intake.
Consistent with this evidence, the 2015 DGAC report de-emphasized the previous recommendation to limit consumption of dietary cholesterol to 300 mg per day, stating that dietary cholesterol is no longer a “nutrient of concern” for Americans [98]. The role of a low-cholesterol diet is discussed in detail elsewhere. (See "Healthy diet in adults", section on 'Low-cholesterol diet'.)
DIETARY FAT ADVICE — Based on advances in evidence, the 2015 Dietary Guidelines Advisory Committee (DGAC) report recommended no upper limit for total dietary fat, and the 2020 DGAC did not re-review this question [1,98]. By contrast, the earlier 2002 Institute of Medicine (IOM) Dietary Reference Intakes (DRIs), which guide the Nutrition Facts panel and other US Department of Agriculture (USDA) panels, have not been updated and recommended limiting total fat intake (for adults, between 20 and 35 percent of energy from fat [2,80]; for 4- to 18-year-olds, 25 to 35 percent; and for children one to three years of age, 30 to 40 percent). The 2020 DGAC report emphasized the importance of quality and types of fat and food sources, as reflected in the following advice:
●Consume less than 10 percent of calories from saturated fat by replacing them with polyunsaturated fat. Only limited evidence supported replacing saturated fat with monounsaturated fat, and replacing saturated fat with carbohydrate was not recommended.
●Keep trans fat consumption as low as possible by limiting foods that contain industrial sources of trans fats, such as partially hydrogenated oils.
●Reduce the intake of calories from solid fats (eg, from meats, butter). Use plant oils to replace these solid fats where possible.
●Replace protein foods that are higher in solid fats (eg, red and processed meats) with choices that are lower in solid fats and calories and/or are sources of oils. These include seafood, legumes (beans and peas), nuts, seeds, plant oils, and soy products, as well as lean meats, poultry, and eggs.
●Health effects of dairy fats remain uncertain and controversial. Most guidelines continue to recommend low-fat dairy products.
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Healthy diet in adults".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topic (see "Patient education: Diet and health (The Basics)")
●Beyond the Basics topic (see "Patient education: Diet and health (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●The evidence suggests that industrial trans fat contributes to the genesis of heart disease, while n-3 polyunsaturated fats and n-6 polyunsaturated fats are protective. It is uncertain whether total saturated and monounsaturated fats have important effects on risk of heart disease, likely due to substantial heterogeneity in subclasses of specific fatty acids and, more importantly, the diversity of food sources of these fats. (See 'Quality of fat' above.)
●Given the heterogeneous effects of different types of fatty acids and food sources, the amount of total fat and perhaps total saturated fat and monounsaturated fat in the diet appear to be less important than the types of foods consumed. (See 'Total fat intake' above.)
●The overall evidence favors limiting processed meats, eating unprocessed red meats in moderation, and consuming plant sources of fats including nuts, seeds, plant oils, avocadoes, and fish. Yogurt and cheese may lower the risk of diabetes. Potentially differing health effects of low- versus full-fat versions remain controversial.
●Fewer data are available regarding the role of intake of fats in the incidence of stroke, cancer, type 2 diabetes, and other outcomes, although most of the evidence suggests results that are consistent with those concerning heart disease
●Reasonable messages that are relatively easy to discuss with patients who do not require special diets for existing diseases (eg, chronic kidney disease, celiac disease, eating disorders) include the following, which are consistent with the 2020 Dietary Guidelines for Americans (see 'Recommendations for patients' above):
•It can be counterproductive to make restriction of total fat a primary recommendation. Concentrate instead on recommending:
-Limiting processed red meats
-Eating unprocessed red meats in moderation (eg, up to one to two portions per week)
-Limiting ultra-processed foods rich in refined starch, added sugars, trans fat, and/or sodium
-Eating more foods rich in healthful fats, vitamins, flavonols, and/or other bioactive compounds such as nuts, seeds, plant oils, fish, fruits, non-starchy vegetables, legumes, and minimally processed whole-grain products
•Do not assume that low-fat or "fat-free" varieties of packaged and processed foods (eg, snack foods, salad dressings) are more healthful or better for weight control.
•When fats are needed for cooking, spreads, dressings, and other uses, recommend plant oils with high amounts of unsaturated fatty acids, including extra virgin olive oil and plant oils containing n-3 polyunsaturated fats such as soybean and canola oils.
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Matthew W Gilman, MD, SM, who contributed to an earlier version of this topic review.
