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Review |
Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts
Address correspondence to: Dr. Frank Hu, Dept. of Nutrition, Harvard School of Public Health, 665 Huntington Ave, Boston, MA 02115. E-mail: Frank.hu{at}channing.harvard.edu
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMAJOR TYPES OF DIETARY...NUT CONSUMPTION AND RISK...INTERVENTION TRIALS OF DIETARY...FISH AND MARINE N-3...ALPHA-LINOLENIC ACID (ALA)THE BALANCE BETWEEN N-3...DIETARY CHOLESTERAL AND EGGSCONCLUSIONSREFERENCES |
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Key words: dietary fat, saturated fat, monounsaturated fat, polyunsaturated fat, trans fatty acids, n-3 fatty acids, cardiovascular disease, coronary heart disease, women
Key teaching points:
• In the past several decades, reduction in fat intake has been the main focus of national dietary recommendations to lower risk of coronary heart disease (CHD).
• Metabolic studies have long established that the type of fat, but not total amount of fat, predicts serum cholesterol levels.
• Results from epidemiologic studies and controlled clinical trials have indicated that replacing saturated fat with unsaturated fat is more effective in lowering risk of CHD than simply reducing total fat consumption.
• Prospective cohort studies and secondary prevention trials have provided strong evidence that a higher intake of n-3 fatty acids from fish or plant sources lowers risk of CHD.
• Recent national dietary guidelines have shifted the emphasis from total fat reduction to distinguishing different types of fat.
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMAJOR TYPES OF DIETARY...NUT CONSUMPTION AND RISK...INTERVENTION TRIALS OF DIETARY...FISH AND MARINE N-3...ALPHA-LINOLENIC ACID (ALA)THE BALANCE BETWEEN N-3...DIETARY CHOLESTERAL AND EGGSCONCLUSIONSREFERENCES |
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It is now increasingly recognized that the low-fat campaign has been based on little scientific evidence and may have caused unintended health consequences. It is also increasingly appreciated that different types of fats have different health effects. In this article, we review epidemiologic evidence and dietary intervention studies regarding the relationship between dietary fat intake and risk of CHD, with particular emphasis on different major types of fat and n-3 fatty acids.
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MAJOR TYPES OF DIETARY FAT |
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TOPABSTRACTINTRODUCTIONMAJOR TYPES OF DIETARY...NUT CONSUMPTION AND RISK...INTERVENTION TRIALS OF DIETARY...FISH AND MARINE N-3...ALPHA-LINOLENIC ACID (ALA)THE BALANCE BETWEEN N-3...DIETARY CHOLESTERAL AND EGGSCONCLUSIONSREFERENCES |
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Data from international comparisons as well as migration studies, although providing evidence for the importance of diet and environmental factors in the cause of CHD, are inadequate in testing specific hypotheses regarding the role of individual dietary components due to confounding by other aspects of diet, physical activity, smoking, obesity and economic development. Prospective cohort studies of individuals, in which diet is assessed prior to the occurrence of disease, are typically considered as the strongest nonrandomized design. Despite the long-standing interest in the diet-heart hypothesis, the number of cohort studies that have directly addressed associations between dietary fat intake and risk of CHD is surprisingly small and the results are not consistent. A significant positive association between saturated fat intake and risk of CHD was found in two studies [5,6], but not in others [7–13]. A significant inverse association between polyunsaturated fat intake and CHD was found in only one study [11], but not in others [7–10,12,13]. The interpretation of these findings is complicated by small study size, inadequate dietary assessment, incomplete adjustment for intake of total energy, failure to account for trans isomers of unsaturated fats and lack of control for intakes of other types of fat and other components of diet.
More recently, using 14-year follow-up data from the Nurses’ Health Study, Hu and colleagues [14] conducted detailed prospective analyses of dietary fat and CHD among 80,082 women aged 34 to 59. The study was particularly powerful because of large sample sizes and repeated assessments of diet. Hu et al. found a weak positive association between saturated fat intake and risk of CHD, but a significant and strong positive association with intake of trans fatty acids. Five percent of energy from saturated fat, compared with equivalent energy from carbohydrates, was associated with a 17 percent greater risk of CHD (relative risk=1.17, 95 percent confidence interval 0.97–1.41, p=0.10). Compared with equivalent energy from carbohydrates, the relative risk for two percent of energy from trans fat was 1.93 (1.43–2.61, p < 0.001); for five percent of energy from monounsaturated fat, 0.81 (0.65–1.00, p=0.05); and for five percent energy from polyunsaturated fat, 0.62 (0.46–0.85, p=0.002). Total fat was intake not significantly related to risk (for five percent energy 1.02, 0.97–1.07, p=0.55). It was estimated that replacement of five percent of energy from saturated fat by unsaturated fats would reduce risk by 42 percent (23–56, p < 0.001), and replacement of two percent of energy from trans fat by unhydrogenated unsaturated fats would reduce risk 53 percent (34–67, p < 0.001) (Fig. 1). These findings challenge the widely recommended low-fat high-carbohydrate diets because they suggest that replacing saturated and trans fats with unhydrogenated unsaturated fats is more effective in preventing CHD than reducing overall fat intake.
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Although stearic acid has little effect on total and LDL cholesterol concentrations compared to carbohydrate, it may lower HDL compared to monounsaturated or polyunsaturated fatty acids, and the HDL-lowering effect of stearic acid was particularly strong among women [18]. Aro et al. [19] recently reported that, compared with myristic and palmitic acids, stearic acid reduced LDL concentration, but also reduced HDL level. Thus, the ratios of LDL to HDL and apo B to apo A-I were not affected. Moreover, stearic acid increased Lp(a) concentration [19] and may activate Factor VII [20] and impair fibrinolysis [21]. These data, along with the findings from the Nurses’ Health Study, suggest that distinguishing stearic acid from other saturated fats in dietary advice to reduce coronary risk does not appear to be justified. Moreover, these saturated fats are highly correlated in typical diets due to shared food sources (e.g., beef and dairy products).
N-6 Polyunsaturated Fat
Numerous metabolic studies have shown strong cholesterol-lowering effects for vegetable oils rich in linoleic acid when substituted for dietary saturated fat [22]. Also, dietary intervention trials using high-polyunsaturated-fat diets have been more effective than those using low-fat high-carbohydrate diets in lowering total serum cholesterol as well as rates of CHD (discussed below) [23]. In prospective cohort studies among men, a strong inverse association for polyunsaturated fat was found in the Western Electric Study [11], and borderline significant inverse associations were found in the Ireland-Boston Heart Study [6] and the usual care group of the Multiple Risk Factor Intervention Trial [24]. The inverse association between polyunsaturated fat and CHD observed in the Nurses’ Health Study is consistent with previous findings, but stronger than predicted by the effects of polyunsaturated fat on blood lipids alone, based on the Keys [25] and Hegested equations [26] derived from metabolic studies. This suggests that n-6 polyunsaturated fat may have other beneficial effects on cardiovascular disease besides improving lipid profile. In animal and metabolic studies, an increased intake of n-6 polyunsaturated fatty acid improves insulin sensitivity [27,28]. In the Nurses’ Health Study, a higher intake of n-6 polyunsaturated fat was associated with a significantly lower incidence of type 2 diabetes [29]. In addition, animal studies have suggested an anti-arrhythmic effect when sunflower oil (rich in linoleic acid) was fed [30], although the effect was less than that when fish oil was fed.
In the Nurses’ Health Study [17], the ratio of polyunsaturated fat to long-chain saturated fatty acids (P:S ratio) was strongly associated with a lower risk of CHD. After adjustment for age, smoking, other nondietary variables and intakes of monounsaturated fat, trans fat, protein and total energy, the RR of CHD was 0.79 (95% CI 0.70–0.89) for each 0.2 unit increment in the ratio. In the categorical analysis, the multivariate RRs across deciles of the ratio (the median values ranged from 0.23 to 0.72 from the lowest to highest deciles) were 1.0 (reference), 0.92, 0.90, 0.87, 0.94, 0.81, 0.68, 0.72, 0.58, and 0.58(0.41–0.83) (p for trend < 0.0001) (Fig. 3). These data suggest that replacing long chain saturated fat with polyunsaturated fat is likely to substantially reduce the risk of CHD. In addition, when intakes of polyunsaturated and trans fat were considered together [14], the lowest risk of CHD was observed among those who were in the lowest quintile of trans fat and the highest quintile of polyunsaturated fat; the RR comparing women in this category with those with highest intake of trans fat and lowest intake of polyunsaturated fat was 0.31 (95% CI 0.11–0.88). These results indicate a substantial benefit to substituting polyunsaturated fat (such as unhydrogenated soybean or corn oil) for trans fat (such as hard margarine) in the diet or other foods high in trans fatty acids.
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Prospective cohort studies that address the association between intake of monounsaturated fat and CHD risk are sparse. Two studies found an increased risk of CHD with a higher intake of monounsaturated fat in younger, but not older participants [32,33]. However, neither study adjusted for intake of other types of fat. A more recent study found an inverse association for monounsaturated fat after adjusting for intakes of other types of fat [12]. Because the main source of monounsaturated fat in the U.S. diet is beef and dairy fats and partially hydrogenated vegetable oils, intake of monounsaturated fat is strongly correlated with saturated and trans fats. Thus, the relative risks for monounsaturated fat intake not adjusted for saturated and trans fats are likely to be seriously confounded. In the Nurses’ Health Study [14], after adjusting for other fats, monounsaturated fat intake was inversely associated with risk of CHD, although the association was weaker than that for polyunsaturated fat.
In metabolic studies, replacing carbohydrates with monounsaturated fat raises HDL without affecting LDL [34]. This replacement may also improve glucose tolerance and insulin sensitivity among patients with diabetes mellitus [35]. In addition, monounsaturated fat is resistant to oxidative modification [36].
The major non-animal sources of monounsaturated fat include olive and canola oils, nuts and avocados. Both canola oil and nuts are also important sources of polyunsaturated fat. In addition, liquid vegetable oils generally contain a higher amount of vitamin E, whereas animal fat contain little antioxidants.
Trans Fatty Acids
The positive relationship between trans fat intake and risk of CHD observed in the Nurses’ Health Study is generally consistent with several prospective studies conducted in men, including the Health Professionals’ Follow-up Study [13] and the Alpha-Tocopherol Beta-Carotene Study [12]. The concentration of trans fatty acids in adipose tissue was not significantly associated with risk of myocardial infarction in the EURAMIC study [37] or with sudden cardiac death in a small case-control study in the United Kingdom [38]. However, the 95% confidence intervals (CIs) for the relative risks in the highest categories of trans-fatty acids in both studies were very wide and included the estimate of relative risk in the Nurses’ Health Study. Also, in the EURAMIC study, after exclusion of an uninformative area (Spain, where trans fat intake was uniformly very low due to high consumption of olive oil), the relative risk for the highest versus the lowest category (1.44, 95% CI 0.94–2.20) was close to that in the Nurses’ Health Study (RR for extreme quintiles=1.53, 95% CI 1.16–2.02).
A higher intake of trans fat can contribute to increased risk of CHD through multiple mechanisms. First, trans fatty acids raise LDL cholesterol levels [39–42] and lower HDL cholesterol [39,41,42] relative to cis unsaturated fatty acids. As such, the increase in the ratio of total to HDL cholesterol for trans fat is approximately double that for saturated fat [43]. Second, trans fat increases lipoprotein (a) levels [44,45], which are positively associated with risk of CHD [46]. Third, trans fat raises plasma triglyceride levels [47], and increased triglycerides are independently associated with increased risk of CHD [48,49]. Fourth, trans fatty acids can adversely affect essential fatty acid metabolism and prostaglandin balance by inhibiting the enzyme delta-6-desaturase and, as a result, may promote thrombogenesis [50–52]. Finally, recent data have suggested that high intake of trans fat may promote insulin resistance in humans [28].
The major sources of trans fatty acids in the U.S. are stick margarine, commercially baked products, and deep fried fast food. In Europe, virtually all margarines have become trans fat free due to rapid response by the manufactures to these health concerns. The change from stick margarine to trans fat free margarine, however, has been slow in the U.S. On the other hand, in the U.S., margarine now accounts for only 25 percent to 37 percent of trans fatty acids; the remainder is "hidden" in baked goods, fried fast foods, and other prepared foods [53]. For example, a medium-size French fries contains 5–6 grams, a doughnut contains 2 grams, and an ounce of crackers contains 2 grams of trans fatty acids [54]. Unfortunately, many of these products do not need to be labeled under the proposed regulations to label trans fatty acids which are now under consideration by the Food and Drug Administration.
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NUT CONSUMPTION AND RISK OF CHD |
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TOPABSTRACTINTRODUCTIONMAJOR TYPES OF DIETARY...NUT CONSUMPTION AND RISK...INTERVENTION TRIALS OF DIETARY...FISH AND MARINE N-3...ALPHA-LINOLENIC ACID (ALA)THE BALANCE BETWEEN N-3...DIETARY CHOLESTERAL AND EGGSCONCLUSIONSREFERENCES |
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Several clinical studies have evaluated the effects of diets high in nuts (including walnuts, peanuts, almonds and other nuts) on blood lipids. In a randomized, controlled study, Sabate and coworkers [58] randomized 18 normocholesterolemic men to either a control or a high walnut diet and then switched after four weeks. Both diets conformed to the National Cholesterol Education Program Step I diet and were identical in foods and macronutrients, except that walnuts provided 20% of calories in the walnut diet (replacing meat, potato chips, oils, margarine and butter). When compared to the control diet, men in the walnut diet decreased total and LDL cholesterol levels by 12% and 16%, respectively. Although there was a slight decrease in HDL cholesterol level (4.9%) in the walnut diet, the ratio of LDL cholesterol to HDL cholesterol was significantly lowered by the walnut diet (12%). A cholesterol-lowering effect was also observed for diets supplemented with almonds [59,60]. In addition, a low-fat diet supplemented with peanuts significantly improved serum lipoprotein profiles compared to a regular low-fat diet among postmenopausal hypercholesterolemic women [61].
The beneficial effects of nut consumption observed in clinical and epidemiologic studies underscore the importance of distinguishing different types of fat. Although nuts are high in fat, the predominant types of fat in nuts are mono- and poly-unsaturated (Table 1), which lower LDL cholesterol level. Other potentially protective constituents in nuts include vegetable protein, magnesium, vitamin E, fiber, and potassium.
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INTERVENTION TRIALS OF DIETARY FAT |
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TOPABSTRACTINTRODUCTIONMAJOR TYPES OF DIETARY...NUT CONSUMPTION AND RISK...INTERVENTION TRIALS OF DIETARY...FISH AND MARINE N-3...ALPHA-LINOLENIC ACID (ALA)THE BALANCE BETWEEN N-3...DIETARY CHOLESTERAL AND EGGSCONCLUSIONSREFERENCES |
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Two earlier secondary prevention trials also used high polyunsaturated-fat diets. The Oslo Diet-Heart Study, which included 21% energy from polyunsaturated fat, found a significant reduction in serum cholesterol and major coronary events (fatal and nonfatal MI) at five years of follow-up [68]. After 11 years, fatal MI was reduced by 44% (p=0.004) and total cardiovascular mortality was reduced by 14% (p=0.13) [69]. Another trial [70] using a high amount of soybean oil found a 16% reduction in serum cholesterol at six months and a 12% (nonsignificant) reduction in the rate of recurrent coronary events over four years. But deaths from cardiovascular disease were not affected by the treatment. In contrast to the favorable results observed in trials using high-polyunsaturated fat diets, two secondary prevention trials testing the approach of total fat reduction did not find a significant reduction in serum cholesterol or CHD events [71,72]. The low-fat intervention group in the Diet and Reinfarction Trial (DART) [72] was unable to achieve the goal set for total fat, raising questions about the compliance of the patients to a low-fat diet.
In the 1990s, two secondary prevention trials using the whole diet approach instead of modification of the amount of dietary fat reported favorable results. The Lyon Diet Heart Study tested the effects of a "Mediterranean" diet enriched with alpha-linolenic acid compared to a standard low fat diet [73]. The intervention diet included more bread, more fruits and vegetables, more fish and poultry and less red meat and butter. After a mean follow-up of 27 months, coronary events were reduced by 73% in the treatment group and total mortality was reduced by 70%. The benefit of the intervention diet was maintained up to four years after the first infarction [74]. Interestingly, blood lipids were not affected by the intervention, but blood levels of n-3 fatty acids, especially alpha-linolenic acid and anti-oxidant vitamins increased significantly in the treatment group.
The Indian Heart Study [75] tested a semi-vegetarian diet enriched with fruits, vegetables, whole grains and nuts among patients during hospitalization with acute myocardial infarction. After 12 weeks of treatment, coronary events were reduced by 36%, and at the end of trial (one year), coronary death was reduced by 41% and nonfatal MI by 38%. In the meantime, serum cholesterol decreased by 8%, systolic blood pressure decreased by 8 mmHg, diastolic decreased by 6 mmHg and body weight decreased by 4 kg.
In both trials, total fat intake did not appreciably change. The success of these trials indicates that the right types of fatty acids and other components of diet are more important than total amount of fat in reducing coronary risk. These trials also support the clinical utility of the overall dietary pattern approach in the prevention of CHD. However, in these trials, it is not possible to determine which of the nutritional changes were responsible for the observed reduction in CHD. Also, both trials were conducted in myocardial infarction patients, and these diets have not yet been tested in the primary prevention of CHD.
Angiographic Trials
Several angiographic trials have examined the effects of dietary intervention on progression of coronary atherosclerosis. In an uncontrolled trial (The Leiden Intervention Trial), Arntzenius and coworkers [76] tested a vegetarian diet with a high ratio of polyunsaturated fat to saturated fat (P:S=2) among 39 patients with stable angina pectoris. There was a significant retardation in coronary lesion growth after two years, which was primarily attributed to improved lipid profile. During the intervention, participants’ linoleic acid content of cholesteryl esters significantly increased. The St. Thomas Atherosclerosis Regression Study (STARS) [77] tested the effects of a dietary intervention with a moderate amount of total fat (27% energy) but relatively high polyunsaturated fat (8% energy). The dietary intervention alone significantly reduced overall progression of coronary narrowing and increased overall regression of coronary artery disease. Adding a cholesterol-lowering medication, cholestyramine, to the dietary intervention further reduced the progression of coronary atherosclerosis.
The combined effects of diet and lifestyle modification on the progression of atherosclerosis have been investigated in several studies. In the Lifestyle Heart Study, Ornish and colleagues [78] assigned 28 MI patients to an intervention group with low-fat, strict vegetarian diet, exercise, stress management and yoga and 20 patients to a usual care group. After one year, blood cholesterol was lowered by 19% and the average percent diameter stenosis was reduced by 5.6% in the intervention group, as compared with the control group. At year five [79], coronary atherosclerosis continued to regress in the experimental group, but to progress in the control group, and significantly more "cardiac events" (MI, percutaneous transluminal coronary angioplasty, coronary artery bypass graft, cardiac hospitalization, deaths) occurred in the control group. The number of "hard endpoints" (MI and deaths), however, was too small to allow for meaningful analyses. Interestingly, in the control group coronary stenosis worsened (28% relative worsening) despite substantial reduction in fat intake (from 31% of energy to 25% of energy) and LDL cholesterol (19% reduction). Thus, it is not clear whether the low-fat dietary component contributed to the regression of coronary atherosclerosis over and beyond exercise and other programs in the intervention. Indeed, in an angiographic trial conducted in Germany, increased exercise was the most important variable that predicted the reduction in coronary stenosis [80]. The low-fat regimen in the Lifestyle Heart Study has been criticized as being extreme and unnecessarily rigid. Even fatty fish and nuts, which have been documented to protect against CHD, are excluded. Poor adherence to such diet is another major concern in the application of such diet to the public.
Two other multifactorial intervention trials have yielded favorable results on progression of atherosclerosis among patients with existing coronary disease [80,81]. Both trials involved a low saturated fat and relatively high polyunsaturated diet (P:S ratio >1) and intensive physical exercise. In the trial conducted in Germany [80], the treatment also comprised intensive physical exercise in group training sessions (minimum, 2 hr/wk) and daily home exercise periods (20 min/day). After 12 months, 32% patients in the intervention group experienced regression of coronary lesions as compared with 17% in the control group. In contrast, 48% patients in the control group experienced progression of coronary lesions as compared with 23% in the treatment group. Besides dietary intervention, the Stanford Coronary Risk Intervention Project (SCRIP) [81] involved exercise, smoking cessation, weight loss and cholesterol-lowering medications. After four years, the rate of narrowing of diseased coronary artery segments in the intervention group was 47% less than that for subjects in the control group. The success of these secondary prevention trials using angiographic endpoints is in direct contrast to the disappointing results from several primary prevention trials of multifactorial approach [82,83]. However, because multiple dietary, lifestyle and even medication changes were made simultaneously in these trials, the interpretation of any observed difference in outcome is complicated. In addition, whether coronary stenosis detected by angiography is a valuable endpoint is not yet settled [84].
In summary, dietary intervention trials in general support the benefit of replacing saturated fat with polyunsaturated fat. Evidence regarding the replacement of total or saturated fat by carbohydrate is more limited, but is generally unsupportive of benefit. These results are consistent with prospective cohort studies and metabolic studies indicating the importance of types of fat. Although the ideal randomized trial of dietary fat and primary prevention of CHD in free-living populations has not been and may never be conducted due to feasibility concerns, the existing evidence powerfully supports the strategy of replacing saturated and trans fats with unhydrogenated unsaturated fats.
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FISH AND MARINE N-3 FATTY ACIDS |
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TOPABSTRACTINTRODUCTIONMAJOR TYPES OF DIETARY...NUT CONSUMPTION AND RISK...INTERVENTION TRIALS OF DIETARY...FISH AND MARINE N-3...ALPHA-LINOLENIC ACID (ALA)THE BALANCE BETWEEN N-3...DIETARY CHOLESTERAL AND EGGSCONCLUSIONSREFERENCES |
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Two interventional studies, the Diet and Reinfarction Trial (DART) [96] and the GISSI-Prevenzione trial [97], have evaluated whether fish consumption or fish oil supplementation reduces coronary mortality among MI patients. The diet and reinfarction trial (DART), which included 2033 men allocated to three dietary interventions, showed that subjects who received fish advice had a significant reduction in total mortality of 29% after two years. While not statistically significant, there was also a trend toward a reduction in recurrent ischemic heart disease events with increased fatty fish consumption. The more recent GISSI-Prevenzione trial randomly assigned 11,324 myocardial infarction patients to four different groups: n-3 fatty acids (850–882 mg EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) (1:2)), vitamin E (330 mg alpha-tocopherol), a combination of n-3 and vitamin E and control. Daily supplementation with n-3 fatty acids resulted in a 10% to 15% reduction in the main endpoints (death, non-fatal MI and stroke). Most of the reduction was attributable to the decrease in cardiovascular death, especially sudden cardiac death. These two trials provide support for a therapeutic role of fish oil in the treatment of MI patients.
The protective effects of marine n-3 fatty acids are probably due to multiple mechanisms, including reducing triglyceride levels [98], reducing platelet aggregation [99] and anti-arrhythmic effects [100]. There is growing evidence to suggest that fish oil may improve endothelial dysfunction, an early marker of atherosclerosis [101,102]. In vitro studies have consistently shown that n-3 fatty acids decrease expression of adhesion molecules on the endothelium and also decrease leukocyte/endothelium interactions [101]. Additionally, clinical experimental studies have shown that n-3 fatty acid supplementation improves endothelial-dependent vasomotor function [102,103].
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ALPHA-LINOLENIC ACID (ALA) |
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TOPABSTRACTINTRODUCTIONMAJOR TYPES OF DIETARY...NUT CONSUMPTION AND RISK...INTERVENTION TRIALS OF DIETARY...FISH AND MARINE N-3...ALPHA-LINOLENIC ACID (ALA)THE BALANCE BETWEEN N-3...DIETARY CHOLESTERAL AND EGGSCONCLUSIONSREFERENCES |
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Experimental studies have suggested an antiarrhythmic effect of ALA. In cell culture studies, the addition of ALA slows the beating rate of isolated neonatal rat cardiac myocytes [112]. In animal experiments in which arrhythmias were induced by coronary occlusion and reperfusion, significant reductions in the incidence of ventricular fibrillation and cardiac mortality were observed in rats fed with ALA-rich diets. In one of the experiments [113], similar significant reductions in cardiac arrhythmia were observed in animals fed red meat supplemented with fish oil and in those fed red meat supplemented with canola oil (8% ALA), when compared to the control group (fed only red meat). Interestingly, mortality was even lower in the canola oil group than in fish oil group (7% vs. 10%). In another experiment [114], mortality due to ventricular fibrillation was significantly lower in rats fed a diet containing canola oil, compared to those fed olive oil. The antiarrhythmic effect of ALA may be attributable to an increased electrical threshold for induction of ventricular fibrillation [114]. In a secondary prevention trial conducted among patients with existing myocardial infarction (Lyon Diet Heart Trial) [73], no sudden death occurred in patients randomized to a Mediterranean diet enriched with ALA, compared with eight deaths in the control group. This study supports an antiarrhythmic effect of ALA in humans although other dietary changes were made simultaneously in this trial.
Several epidemiologic studies have examined the association between ALA intake and risk of CHD. In the usual care group of the Multiple Risk Factor Intervention Trial [24], men in the highest quintile of ALA intake (expressed as percent of energy) had a 40% lower CHD mortality compared to men in the lowest quintile. In the Health Professionals Follow-up Study [13], a 1% increase in linolenic intake (expressed as percent of energy) was associated with a 40% lower risk of fatal CHD. In the Finnish Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study [12], men in the highest quintile of energy-adjusted ALA intake had 25% lower CHD mortality. In these three studies, however, the association between ALA intake and CHD was not the main focus, and none were adequately adjusted for other dietary factors, including intakes of other fats, dietary vitamins, folate and vegetables.
Recently, Hu and colleagues examined the relation of ALA intake to incidence of fatal CHD during 10 years of follow-up in the Nurses’ Health Study [115]. After adjusting for coronary risk factors, the RRs of fatal CHD from the lowest to highest quintiles of ALA intake were 1.0, 0.89, 0.90, 0.66, and 0.52 [95% CI 0.30–0.90], p for trend=0.01. The major contributors of ALA in the Nurses’ Health Study were oil and vinegar (e.g., Italian salad dressing) and mayonnaise salad dressings; these products are typically made with soybean oil, which contains approximately 7% ALA if it is not hydrogenated. Hu et al. [115] found an approximately 50% lower risk of fatal CHD among women who consumed oil and vinegar salad dressing frequently (five to six times or more a week) compared to those who consumed this salad dressing less than once a month, after adjusting for vegetable consumption.
Given the strong evidence to support beneficial effects of ALA on cardiovascular disease, flaxseed as well as other important dietary sources of ALA (e.g., unhydrogenated canola and soybean oils and walnuts) (Table 3) can be incorporated into a healthy and balanced diet for the prevention of cardiovascular disease [116]. This is especially important for those choosing not to consume fish. The above findings also raise concern that the widespread promotion of fat-free salad dressings and mayonnaise, a primary source of ALA in the U.S. diet, may have an adverse effect on CHD rates.
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THE BALANCE BETWEEN N-3 AND N-6 POLYUNSATURATED FATTY ACIDS |
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TOPABSTRACTINTRODUCTIONMAJOR TYPES OF DIETARY...NUT CONSUMPTION AND RISK...INTERVENTION TRIALS OF DIETARY...FISH AND MARINE N-3...ALPHA-LINOLENIC ACID (ALA)THE BALANCE BETWEEN N-3...DIETARY CHOLESTERAL AND EGGSCONCLUSIONSREFERENCES |
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Because ALA and its metabolite, EPA, can decrease generation of thromboxane A2, a pro-aggregatory vasoconstrictor, through their inhibitory action on the conversion from linoleic acid to arachidonic acid and the activity of enzyme cyclooxygenase [112,119–121], it is expected that a greater ratio of ALA to linoleic acid will lower risk of CHD, through decreasing thrombotic tendency. However, the prostanoid pathway is only one mechanism through which dietary fatty acids influence the development of CHD. The primary mechanism by which n-6 polyunsaturated fat lowers risk of CHD is through lowering LDL cholesterol, although n-6 fatty acids may also have other beneficial effects, such as improving insulin sensitivity [28] and lowering the threshold for ventricular fibrillation [121]. Because both n-6 and n-3 fatty acids are associated with a lower risk of CHD, although through different biological pathways, the ratio is only weakly related to CHD risk. Nevertheless, it is generally agreed that the ratio of n-3 to n-6 fatty acids in the U.S. diet is less than optimal and should be improved. The point of controversy lies in how to improve the ratio. Although most researchers have proposed to increase the consumption of n-3 fatty acids from both fish and plant sources, others have suggested a reduction in consumption of n-6 fatty acids [122]. Considering the strong protective effect of n-6 polyunsaturated fat against CHD observed in epidemiologic studies and clinical trials, the latter strategy does not seem justifiable. On the contrary, available data strongly support the strategy of replacing animal and hydrogenated fats with natural liquid vegetables oils, which contain both monounsaturated and polyunsaturated fats, in reducing risk of CHD. Such replacement can also increase the intake of n-3 fatty acids because several vegetable oils including canola and soybean oils contain a substantial amount of ALA. Meanwhile, an increase in fish consumption to at least two servings per week has been recommended for the prevention of CHD [123]. These strategies will substantially increase the absolute amount of n-3 fatty acids in the diet and help to achieve a more desirable ratio of n-3 to n-6 fatty acids, without sacrificing the benefit of n-6 polyunsaturated fat.
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DIETARY CHOLESTERAL AND EGGS |
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TOPABSTRACTINTRODUCTIONMAJOR TYPES OF DIETARY...NUT CONSUMPTION AND RISK...INTERVENTION TRIALS OF DIETARY...FISH AND MARINE N-3...ALPHA-LINOLENIC ACID (ALA)THE BALANCE BETWEEN N-3...DIETARY CHOLESTERAL AND EGGSCONCLUSIONSREFERENCES |
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To avoid elevations in blood cholesterol and reduce CHD risk, the public has been advised to consume no more than 300 mg cholesterol daily and limit consumption of eggs, which contain about 213 mg cholesterol per egg [131,132]. In controlled metabolic studies, ingestion of cholesterol by feeding egg yolks or whole eggs raises blood total and LDL cholesterol levels [126–128,133]. In most egg feeding studies, intakes of other nutrients such as fatty acids, carbohydrates and protein were balanced between egg and no-egg groups so that only dietary cholesterol varied. Therefore, these studies did not really examine the impact of ingestion of eggs per se on blood lipids.
Surprisingly, there is little direct evidence linking higher egg consumption and increased risk of CHD. In the Framingham study, Dawber and colleagues [134] found no significant association between egg consumption and incidence of CHD despite a wide range of egg intake. In an earlier analysis of the Seventh-Day Adventists study [135], higher egg consumption appeared to be associated with increased risk of fatal CHD, but this association was not present in a more recent analysis with a longer follow-up [136]. In a case-control study conducted in Italy [137], the frequency of egg consumption was not significantly associated with risk of CHD in women. In a detailed analysis of egg consumption and incidence of CHD among 117,933 apparently healthy subjects in the Nurses’ Health Study and Health Professionals’ Follow-up Study, Hu and colleagues [138] found no evidence of an overall positive association between egg consumption and risk of CHD in either men or women. The relative risks (RRs) of CHD across categories of intake (<1/week, 1/wk, 2–4/week, 5–6/week, >=1/day) were 1.0, 1.06, 1.12, 0.90, and 1.08 (p for trend=0.75) in men and 1.0, 0.82, 0.99, 0.95, and 0.82 (p for trend=0.95) in women.
The null association between egg consumption and risk of CHD observed in these studies may be somewhat surprising, considering the widespread belief that eggs are a major cause of heart disease. One egg contains about 200 mg cholesterol, but also appreciable amounts of protein, unsaturated fats, folate, B vitamins and minerals. It is conceivable that the small adverse effect caused by cholesterol is counterbalanced by potential beneficial effects of other nutrients.
One potential alternative explanation for the null finding is that background dietary cholesterol may be so high in the usual Western diet that adding somewhat more has little further effect on blood cholesterol. In a randomized trial, Sacks et al. [139] found that adding one egg per day to the usual diet of 17 lactovegetarians whose habitual cholesterol intake was very low (97 mg/day) significantly increased LDL cholesterol level by 12%. In a meta-analysis of controlled metabolic studies, Hopkins [140] found that serum cholesterol’s response to added dietary cholesterol is modulated by baseline cholesterol intake. The higher the baseline cholesterol intake, the less the response induced by adding cholesterol to the diet. In the analyses conducted by Hu et al. [138], differences in non-egg cholesterol intake did not appear to be an explanation for the null association between egg consumption and risk of CHD. However, the possibility that egg consumption may modestly increase the risk among participants with very low background cholesterol intake cannot be excluded.
These findings do not suggest that one should go back to the traditional high cholesterol Western diet. Instead, they suggest that among healthy men and women, moderate egg consumption can be part of a nutritious and balanced diet. Because eggs are excellent and relatively inexpensive sources of essential amino acids and certain vitamins, they can substitute for other animal products such as red meat. These results also illustrate the danger of judging health effects of a food by single nutrients or components contained in the food.
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TOPABSTRACTINTRODUCTIONMAJOR TYPES OF DIETARY...NUT CONSUMPTION AND RISK...INTERVENTION TRIALS OF DIETARY...FISH AND MARINE N-3...ALPHA-LINOLENIC ACID (ALA)THE BALANCE BETWEEN N-3...DIETARY CHOLESTERAL AND EGGSCONCLUSIONSREFERENCES |
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A major purported benefit of a low-fat diet is weight loss. But long-term clinical trials have not provided convincing evidence that reducing dietary fat can lead to substantial weight loss [141]. On the contrary, there is some evidence that a diet containing a high amount of refined carbohydrates may increase hunger and promote overeating, which can lead to weight gain and obesity [142]. It is now generally agreed that total energy intake, whether from fat or carbohydrate, relative to energy expenditure, is a more important determinant of body weight than dietary fat per se.
It has been increasingly recognized that the widely promoted low-fat concept is too simplistic and not compatible with available scientific data. In this context, the recently revised national dietary guidelines [123,143] have de-emphasized the role of total fat in the prevention of CHD and other chronic diseases. In particular, the 2000 Dietary Guidelines for Americans recommend the public to "choose a diet that is low in saturated fat and cholesterol and moderate in total fat", which is modified from the recommendation to "choose a diet low in fat, saturated fat and cholesterol" stated in the 1995 edition of the guidelines. But the revised guidelines have inherited the recommendation of no more than 30% of calories from fat from previous editions of the guidelines. Also, in the food guide pyramid, all fats and oils are still lumped together on the top with no distinguishing of different types of fat. The revised 2000 American Heart Association (AHA) dietary guidelines have gone a step further to eliminate the upper limit of 30% of calories from fat as a major dietary recommendation to prevent cardiovascular disease. Moreover, the AHA major guidelines recommend the public to substitute unsaturated fatty acids from vegetable oils, fish, nuts and legumes for saturated and trans fatty acids. These guidelines, if followed, can have substantial potential in further reducing rates of CHD in the U.S. However, due to the campaign against total fat over the years, the belief that "fat is bad" has been strong and widespread. Thus, great educational efforts are needed to communicate nutritional messages about the health effects of different types of fat to the public and to translate current dietary recommendations into dietary practice as well.
Received November 2, 2000. Accepted November 22, 2000.
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TOPABSTRACTINTRODUCTIONMAJOR TYPES OF DIETARY...NUT CONSUMPTION AND RISK...INTERVENTION TRIALS OF DIETARY...FISH AND MARINE N-3...ALPHA-LINOLENIC ACID (ALA)THE BALANCE BETWEEN N-3...DIETARY CHOLESTERAL AND EGGSCONCLUSIONSREFERENCES |
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-Linolenic Acid Content of Various Oils and Foods