Fats (for Parents)
be more specific in dietary recommendations on the relationship between SFA and CVD. Fats, oils and lipids consist of a large number of organic compounds, including . Figure 2: Fatty acid profile of dietary fat present in selected foods. Evolutionary and Historical Perspectives Concerning Edible Lipids for Human connection of excess consumption of omega-6 fatty acid to the marked In the foods consumed by our ancestors, the fats and oils came from. Dairy foods – such as butter, cream, full fat milk and cheese products: Palm oil; Coconut; Coconut milk and cream; Cooking margarine.
The double bonds in unsaturated fatty acids, like other types of double bonds, can exist in either a cis or a trans configuration. In the cis configuration, the two hydrogens associated with the bond are on the same side, while in a trans configuration, they are on opposite sides see below. A cis double bond generates a kink or bend in the fatty acid, a feature that has important consequences for the behavior of fats.
Saturated fatty acid example: Unsaturated fatty acid examples: Saturated fatty acids tails are straight, so fat molecules with fully saturated tails can pack tightly against one another. This tight packing results in fats that are solid at room temperature have a relatively high melting point.
In contrast, cis-unsaturated fatty acid tails are bent due to the cis double bond. This makes it hard for fat molecules with one or more cis-unsaturated fatty acid tails to pack tightly. So, fats with unsaturated tails tend to be liquid at room temperature have a relatively low melting point — they are what we commonly call oils.
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For instance, olive oil is mostly made up of unsaturated fats 2 2. Trans fats are rare in nature, but are readily produced in an industrial procedure called partial hydrogenation.
In this process, hydrogen gas is passed through oils made mostly of cis-unsaturated fatsconverting some — but not all — of the double bonds to single bonds. Trans-unsaturated fatty acids can pack more tightly and are more likely to be solid at room temperature. Partial hydrogenation and trans fats might seem like a good way to get a butter-like substance at oil-like prices. Unfortunately, trans fats have turned out to have very negative effects on human health.
Because of a strong link between trans fats and coronary heart disease, the U. Food and Drug Administration FDA recently issued a ban on trans fats in foods, with a three-year deadline for companies to remove trans fats from their products 4 4.
Omega fatty acids Another class of fatty acids that deserves mention includes the omega-3 and omega-6 fatty acids. There are different types of omega-3 and omega-6 fatty acids, but all of them are made from two basic precursor forms: Some fish, such as salmon, and some seeds, such as chia and flax, are good sources of omega-3 fatty acids.
Omega-3 and omega-6 fatty acids have at least two cis-unsaturated bonds, which gives them a curved shape. Omega-6 fatty acids are defined analogously, with the first double bond located between the sixth and seventh carbons from the omega end. Image of alpha-linoleic acid ALAshowing its curled shape due to its three cis double bonds.
Omega-3 and omega-6 fatty acids play a number of different roles in the body. They are precursors starting material for the synthesis of a number of important signaling molecules, including ones that regulate inflammation and mood. Omega-3 fatty acids in particular may reduce the risk of sudden death from heart attacks, decrease triglycerides in the blood, lower blood pressure, and prevent the formation of blood clots. However, fats are essential to the body and have a number of important functions.
For instance, many vitamins are fat-soluble, meaning that they must be associated with fat molecules in order to be effectively absorbed by the body. Fats also provide an efficient way to store energy over long time periods, since they contain over twice as much energy per gram as carbohydrates, and they additionally provide insulation for the body. Like all the other large biological molecules, fats in the right amounts are necessary to keep your body and the bodies of other organisms functioning correctly.
Waxes Waxes are another biologically important category of lipids. Wax covers the feathers of some aquatic birds and the leaf surfaces of some plants, where its hydrophobic water-repelling properties prevent water from sticking to, or soaking into, the surface.
Image of shiny leaf surface covered with wax. Structurally speaking, waxes typically contain long fatty acid chains connected to alcohols by ester linkages, although waxes produced by plants often have plain hydrocarbons mixed in as well 6 6.
Phospholipids What keeps the watery goo cytosol inside of your cells from spilling out? The apolipoproteins serve both structural and functional roles. Some apoproteins are ligands for specific cell surface receptors, e.
For reviews of lipoprotein structure and metabolism, see Havel and Stanbury et al. Relationship of Plasma Lipid and Lipoprotein Levels to Atherosclerotic Cardiovascular Diseases Epidemiologic Evidence for CHD Most major epidemiologic studies have focused on white men, but a few have provided information about women and nonwhites of both sexes.
Total Cholesterol TC TC is used in this chapter as an abbreviation for the total cholesterol in either serum or plasma. Although this difference should be considered in comparing the results of studies with one another when numbers of subjects are large and small systematic biases might affect the comparison, it does not affect the major results or conclusions of studies discussed in this report in which serum or plasma is used in analyses of cholesterol. Thus, TC is used interchangeably for both serum and plasma total cholesterol.
Until the past decade, TC, rather than lipoprotein cholesterol, was measured in most epidemiologic studies because reliable methods for measuring lipoprotein cholesterol in large numbers of people were not available. Therefore, most data on disease risk are based on TC level. In the Seven Countries Study, investigators studied 16 populations of middle-aged men residing in seven countries: Examination methods, laboratory procedures, and quality control procedures were standardized.
Similar differences were found some 15 years later for male and female adolescents and adults in the Jerusalem Lipid Research Clinics Prevalence Study Halfon et al. Other differences among populations have been observed for men in Puerto Rico, Hawaii, and Framingham, Massachusetts Gordon et al. Some of this evidence is reviewed in the report of a Conference on Health Effects of Blood Lipoproteins The results of these various studies, particularly the studies of migrants, indicate that the differences in mean TC levels among populations are due largely to environmental factors, principally diet, rather than to constitutional factors.
Large population differences in mean TC levels have also been observed among children and adolescents; the pattern of variation in these means closely parallels that of the adult values, but at lower absolute values Conference on Blood Lipids in Children, Variation in CHD Rates Among Populations Large differences also exist among populations in the incidence of and mortality from CHD and in the prevalence and severity of atherosclerosis. For example, in the Seven Countries Study, age-standardized, year incidence of first major CHD events myocardial infarction and coronary death among men free of CHD at entry varied from 3 in 1, on Crete to in 1, in eastern Finland Keys, b.
Corresponding figures for year CHD mortality were 0 and 68 in 1, respectively. Variation in Atherosclerosis Among Populations In the International Atherosclerosis Project, the extent of atherosclerosis in the coronary arteries and aortas was measured in 23, autopsied people from 19 populations in 14 countries McGill, b.
Differences among populations were noticeable at ages 15 to 24 and marked at ages 25 to With few exceptions, ranking the populations according to extent of raised lesions corresponded closely to ranking them by CHD mortality rate.
The correlations between median TC and national CHD death rates for these seven countries at 0, 5, 10, and 15 years after TC was measured were. In the International Atherosclerosis Project, there was a correlation of.
These results support the conclusion that variation in CHD rates among populations is determined predominantly by differences in levels of TC. The association may be weak or absent in some populations with low mean levels of TC and low absolute risk of CHD, e. In fact, questions have been raised as to whether the association of serum TC with CHD risk is continuous or whether there is some level of serum TC below which it is not related to risk of CHD e. In four of the eight studies in the U.
In the same study, however, the corresponding 7-year CHD mortality rates previously showed a steadily increasing pattern: The data for that trial are shown in Figure From Martin et al. Results from the observations of screenees in the Multiple Risk Factor Intervention Trial also indicated that the association between TC and 5-year risk of CHD death for 23, black men was similar to that forwhite men Neaton et al.
In the pooled results of five U. This observation has sometimes been misinterpreted to mean that the level of TC is relatively unimportant in elderly people. The committee believes that this misinterpretation may arise from failure to distinguish between the concepts of relative risk the ratio between two risks and attributable risk the difference between two risks. The former is commonly used to evaluate the magnitude of an epidemiologic association; the latter is commonly used to evaluate its public health importance.
In fact, in the set of studies cited above, the attributable risk calculated as the difference in risk between the highest and lowest quintiles did not vary consistently with age. Thus, the corresponding attributable risks were 46, 28, 40, and 42 per 1, in 8 years for men ages 45 to 49, 50 to 54, 55 to 59, and 60 to 64, respectively. Atherosclerosis at Autopsy TC measured by standardized procedures in apparently healthy men was strongly associated with extent of atherosclerosis at autopsy in the Hiroshima Adult Health Study Rickert et al.
There are few data on women. In the Framingham Study, the extent of coronary atherosclerosis in men was positively correlated with TC measured 1, 5, and 9 years before death; in women, only TC measured 9 years before death but not TC measured 5 and 1 years before death correlated significantly Feinleib et al. In a follow-up of the initial report, Freedman et al.
As anticipated, blacks had more extensive fatty streaks than did whites, but there also was a strong positive association between the extent of aortic fatty streaks and the LDL cholesterol concentration within each race group. In summary, epidemiologic findings among populations and for individuals within populations consistently indicate a strong, continuous, and positive relationship between TC levels and the prevalence and incidence of, as well as mortality from, atherosclerotic CHD.
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This relationship has been confirmed in autopsy studies. Few early studies included measurements of lipoprotein cholesterol because of technical difficulties and cost.
In a study of schoolboys 6 to 7 years old selected from 26 rural and urban populations in 16 countries Knuiman et al. The basis for these different results is not clear.
In one study, a correlation of. Knuiman and West obtained standardized measurements of HDL-C in a survey of small samples of men in 13 countries and found a correlation of.
Thus, the extent to which variation among populations in CHD rates may be affected by associated with variations in mean HDL-C levels is uncertain. In the Oslo Study of men ages 40 to 49 years at entry in andantemortem measurements of plasma lipids and other characteristics were available for men for whom there were also postmortem measurements of the extent of atherosclerosis.
The percentage of the coronary intimal surface involved with raised lesions was positively correlated with TC. Although changes in HDL-C are related to changes in CHD risk in most populations, the benefit that can be expected from raising HDL as a preventive strategy in itself is not entirely clear.
Added benefit, over that derived from lowering LDL, is suggested, however, by the long-term results of the Coronary Drug Project Canner et al. The strength of the association was not significantly improved by adding TC or HDL-C to the equation containing this ratio Castelli et al.
The authors concluded that ratios can be useful predictors of risk, but warned that they may not always be as informative as the joint use of the two individual figures used to calculate the ratio. It seems reasonable to expect that increasing knowledge about the various classes and subclasses of lipoproteins will lead to improved ability to predict risk of atherosclerotic diseases. Whether these prediction formulas will take the form of ratios or more detailed specifications of lipoprotein levels is uncertain.
The recent report of the National Cholesterol Education Program identified the absolute level of LDL-C as the key index for clinical decision-making about cholesterol-lowering therapy and as the specific target for therapy.
The authors of the report stated, ''Reliance on a ratio of either total or LDL-cholesterol to HDL-cholesterol as a key factor in decisions regarding treatment is not a practice recommended in this report. Blood pressure and smoking are not combined into a single number because the clinician needs to know both facts separately in order to recommend an intervention. Similarly, HDL-cholesterol and LDL-cholesterol are independent risk factors with different determinants, and combining them into a single number conceals information that may be useful to the clinician" National Cholesterol Education Program, In summary, of the lipoprotein fractions, LDL has the strongest and most consistent relationship to individual and population risk of CHD.
HDL has generally been found to be inversely associated with risk of CHD in individuals within a population, but in at least three long-term population studies, this inverse association was not seen Keys et al.
Fats and oils
These findings together with the results of animal experiments and clinical research reviewed later in this chapter strongly support the conclusions that LDL-C is centrally and causally important in the pathogenic chain leading to atherosclerosis and CHD. Variation in LDL-C levels explains a large part of individual risk within high-risk cultures and explains almost all the differences in CHD rates among populations. Data are inadequate to characterize ratios of LDL to HDL as a major determinant of the atherosclerotic disease burden among populations; however, the ratio provides improved individual prediction, again within high-risk, high-LDL cultures.
Apolipoproteins Apolipoproteins play key roles in both the structure and function of plasma lipoproteins. Research on the molecular structure, genetic variability, and metabolism of plasma apolipoproteins has progressed rapidly in recent years, particularly with the application of the new techniques of molecular biology.
Knowledge about apolipoproteins has added greatly to our understanding of lipoprotein metabolism and how it is related to atherosclerosis. In a number of instances, genetically controlled variations in apolipoproteins affect lipoprotein structure, composition, and metabolism. For example, polymorphic forms of apolipoprotein E apo E interact with dietary fats to influence plasma lipoprotein concentrations, and assessment of apo E phenotypes is an essential procedure in the diagnosis of familial dysbetalipoproteinemia.
However, the evidence currently available does not clearly show that plasma apolipoprotein levels are better predictors of CHD than are the plasma levels of cholesterol in the major lipoprotein classes. The apo E phenotypes were shown to be due to segregation of three alleles at a single locus Zannis and Breslow, and the major isoforms to be determined by substitution of the amino acid cysteine for arginine Weisgraber et al.
The three major isoforms are called apo E2, E3, and E4.
Fats and Oils: Why We Love Them
Most people with this phenotype do not have familial dysbetalipoproteinemia, however, and in fact have lower plasma cholesterol levels than the general population see Davignon et al. Thus, a single amino acid substitution in one apolipoprotein can have a substantial effect on plasma cholesterol concentrations and on the plasma lipoprotein profile.
This topic has been reviewed thoroughly by Davignon et al. The Apolipoproteins and Atherosclerosis In the s, the availability of better methods for fractionating lipoproteins, for measuring serum apolipoproteins, and for detecting apolipoprotein variants made possible a new series of studies that sought relationships among lipoproteins, apolipoproteins, and atherosclerosis.
This topic was reviewed by Brunzell et al. However, these investigators were not in agreement about whether apolipoprotein levels or lipoprotein cholesterol levels were better indicators of CHD. Wallace and Anderson concluded their review by stating that apolipoprotein levels appeared promising as predictors of CHD, but that large cohort studies would be required to determine whether they are better predictors of atherosclerotic disease than plasma lipoprotein lipid levels and whether they are useful clinically.
Lp a and Human Atherosclerosis The role of lipoprotein a [Lp a ] in atherosclerosis and atherosclerotic heart disease has been controversial ever since Lp a was discovered by Berg The apoprotein of Lp a has been shown to consist of two peptides—apo a and apo B—linked by one or more disulfide bonds Gaubatz et al.
Overall, the evidence concerning the association of Lp a with atherosclerosis is rather scanty, but highly suggestive. Lp a levels in plasma are generally believed not to be affected by diet. Hoff and associates have demonstrated the presence of apo B, apo A-I, and apo C in the arteries of humans and several animal species Hoff and Gaubatz, ; Hoff et al.
The same investigators quantified apo B in lesions Hoff et al. LDL in lesions stimulated the production of cholesteryl esters by macrophages Clevidence et al. These studies clearly show that apo B-containing lipoproteins accumulated in atherosclerotic lesions. LDL from atherosclerotic lesions contained particles larger than those found in plasma LDL, was more electronegative, and stimulated cholesterol esterification in mouse peritoneal macrophages.
The extent to which these alterations in LDL occurred in the arterial intima, after the LDL had entered the vessel wall, is not clear. This combined evidence implicates apo B-containing lipoproteins in the pathogenesis of atherosclerosis. Apolipoproteins and Dietary Responsiveness In view of the critical roles of apolipoproteins in lipoprotein metabolism, genetic variants in addition to those of apo E probably influence the lipemic responses of individuals to dietary fats and thereby affect the risk of CHD.Fats - Types Of Fats - What Is Saturated Fat - What Is Unsaturated Fat - Omega 3's And Omega 6"s
This research area is quite active, and new findings are likely to be available in the near future. Summary Apolipoproteins show promise of helping us to understand the mechanisms linking diet to atherosclerosis and cardiovascular disease, but as yet they have not provided predictive power for atherosclerotic diseases beyond that provided by plasma lipid and lipoprotein cholesterol concentrations. They are not now useful in assessing the relationship of dietary fats to atherogenesis or atherosclerotic cardiovascular diseases on a population-wide basis.
Nonfasting triglyceride levels were measured in the Framingham, Honolulu, and Puerto Rico studies. Results indicated that relatively high mean nonfasting triglyceride levels are compatible with low-population CHD rates when the mean TC is also low Gordon et al. However, in most populations found to have low average TC levels, triglyceride levels are also low Conference on Health Effects of Blood Lipoproteins, Differences Among Individuals A fairly large number of epidemiologic studies have explored relationships between plasma triglyceride levels and the risk of CHD.
The studies conducted before were reviewed in full by Hulley et al. In almost all reported studies, a significant positive association between triglyceride levels and CHD was found upon univariate analysis. However, triglyceride has not held up as an independent risk factor in most of the studies that have provided multivariate adjustment for a full set of major risk variables. It is well established that a reciprocal relationship generally exists, both within populations and within individuals, between plasma triglyceride and, therefore, VLDL and HDL levels.
Thus, individuals with high triglyceride levels tend to have lower HDL levels, and an increase or decrease in triglyceride level in a patient is generally accompanied by an opposite change in HDL-C level. On the other hand, our understanding of the association of VLDL and VLDL remnants to atherosclerosis is still incomplete, and there is some evidence that the latter particles may have an important role in atherogenesis. Hence, the answer to the question of whether or not elevated triglyceride and VLDL levels are causally linked to atherosclerotic disease in some patients, or groups of people, is not clear.
What is clear is that, as a group, people with high triglyceride levels have elevated coronary risk. Overall, however, the potential atherogenicity of the triglyceride-rich lipoproteins has not been determined. For reviews and reports of recent studies, see Aberg et al. Several studies have observed that triglycerides and VLDL may have independent predictive power for CHD in women and a greater association with peripheral arterial disease than with CHD, but none of the associations found was strong Aberg et al.
The National Institutes of Health NIH Consensus Conference on Treatment of Hypertriglyceridemia concluded, "Careful evaluation of existing data indicates that in the presence of normal cholesterol levels mild elevations of plasma triglycerides do not necessarily increase the risk of CVD. Dietary intervention is the primary approach to therapy in these patients, but drugs have a role in selected individuals not responding to dietary management. The Committee on Diet and Health endorses these conclusions.
Summary The relationship between plasma triglyceride levels and cardiovascular diseases is somewhat controversial and unclear. In most within-population studies, plasma triglyceride levels were positively associated with increased risk for cardiovascular diseases but they were not independently predictive for CHD after statistical adjustment for closely associated -attributes such as TC, HDL-C, hypertension, cigarette smoking, and obesity.
As indicated above, however, in the Framingham Heart Study the plasma triglyceride level was found to be an independent predictor of CHD in women. Even so, the plasma total triglyceride level, rather than being a direct cause of atherosclerotic disease, probably reflects the presence of certain atherogenic lipoproteins. It is well known that VLDLs are highly heterogeneous; a number of different kinds of lipoprotein particles are contained within this density class.
Many disease entities that elevate triglyceride levels, such as diabetes mellitus, nephrotic syndrome, chronic renal disease, and certain primary hyperlipidemias, carry an increased risk of CHD. In these situations, the high triglyceride level may be a clue to the presence of other lipoprotein abnormalities that are more directly associated with CHD, such as low HDL-C, elevated apo B or LDL-C, or atherogenic remnant triglyceride-rich lipoprotein particles that have not been well defined.
Thus, whether or not VLDL and triglycerides are directly involved in the atherogenic process, elevated levels can be helpful in identifying people at increased risk of cardiovascular diseases. Clinical-Genetic Evidence of CHD A number of genetic disorders of lipoprotein metabolism have been identified and characterized Brown and Ginsberg, ; Stanbury et al.
The study of these disorders has provided many insights into the structure, metabolism, and regulation of the plasma lipoproteins and apolipoproteins. Several of these disorders are characterized by severe hypercholesterolemia and premature atherosclerosis and CHD.
Such disorders include familial hypercholesterolemia FHfamilial combined hyperlipidemia, and familial dysbetalipoproteinemia type 3 hyperlipoproteinemia. The defective gene results in the receptor being either absent or nonfunctional. One gene for the LDL receptor normally is inherited from each parent. Heterozygous FH occurs in the general population at a frequency of about 1 inmaking FH one of the most common single-gene-determined diseases in humans.
Rarely, about once per million people, individuals inherit two abnormal genes for LDL receptors and hence are homozygous for FH. Severe and often fatal coronary disease frequently develops while these people are in their teens.
One homozygote had an acute myocardial infarction as early as 18 months of age; another died of an acute myocardial infarction at 3 years of age. Very few FH homozygotes survive past age 30 Goldstein and Brown, These rabbits have very high TC and LDL-C levels and develop severe atherosclerosis that is similar to that seen in humans.
This genetic animal model provides further strong evidence of the causal relationship between high LDL-C levels and atherosclerosis. The research on FH and on the LDL receptor has provided insights into the mechanisms that might be involved in the more common problem of the mild to moderately elevated blood cholesterol levels that are seen in the general population. Potential relationships between LDL receptors, diet, and atherosclerosis have been discussed by Brown and Goldstein It is likely that the dietary components that raise plasma TC and LDL-C levels specifically, dietary SFAs and cholesterol, as discussed in detail later in this chapter act, at least in part, by suppressing hepatic LDL receptor activity.
Recent studies Spady and Dietschy, in hamsters powerfully demonstrate the role of dietary saturated triglycerides in augmenting the effect of dietary cholesterol in suppressing hepatic LDL receptor activity and elevating plasma LDL-C levels. Clinical Trials of CHD Small-Scale Trials Angiographic End Points Evidence has been accumulating and a number of studies are under way to determine the effect of lowering TC by diet, drugs, or ileal bypass surgery on the progression or regression of atherosclerotic lesions of coronary and large peripheral arteries as determined by angiography and ultrasound.
As shown angiographically, in the earliest reported randomized controlled trial, patients with intermittent claudication had less angiographic progression and more regression of plaques in the diet- and drug-treated group than did a control group over a month period. In a recently completed randomized controlled trial in which angiographic techniques were used, patients treated with diet and several TC-lowering drugs had less progression and more actual regression of plaques in natural and bypass graft coronary vessels compared to controls over a 2-year period Blankenhorn et al.
These results and those of other systematic studies cited below are generally consistent with the conclusion that reducing LDL-C in hyperlipidemic patients reduces the rate of progression and can induce regression of atherosclerosis according to the degree of blood lipid reduction Arntzenius et al. Key elements of their designs are summarized in Table In five trials, various methods were used to change the plasma lipid concentrations as the only intervention; in two, diet was used; and in three, drugs.
The other four studies, in which diet was also used, were multifactorial trials in which effects of change in plasma lipids were confounded with effects of change in cigarette smoking and blood pressure.
Only one of the six trials involving change in diet—the Los Angeles Veterans Administration Domiciliary Study—was conducted under double-blind conditions Dayton et al.
In the others, individuals were randomized. The number of participants in these studies varied from approximately to nearly 50, A negative sign here indicates that the experimental group had a lower mean level than the control group.
These results indicate that the magnitude of the difference in risk of CHD varied directly with the magnitude of the difference in mean TC. Studies that achieved little or no difference in mean TC had little or no difference in rate of CHD, whereas studies that achieved larger difference in mean TC experienced larger differences in CHD rates. Combined with the evidence from epidemiologic, clinical, and laboratory animal studies, this body of evidence establishes unequivocally that lowering serum TC, particularly LDL-C, reduces the incidence of CHD in middle-aged, hypercholesterolemic men.
High-risk populations were used in most of these studies for quite practical reasons; the cost and problems of conducting such a trial in the general population would be very large and the results might well be inconclusive. Results of the Los Angeles Veterans Administration Domiciliary Trial support the inference that the conclusion may extend to people over 65 years of age as well, perhaps with a somewhat smaller effect, but the evidence bearing on this important question is still weak.
Most of the trials listed in Tables and showed an excess of non-CHD deaths in the intervention group as compared to the comparison group. How much of this can be attributed to chance and whether any of it reflects adverse effects of intervention are complex questions that may never be completely resolved. An analysis of 20 randomized controlled clinical trials that involved change in serum TC as the only systematic intervention indicates no statistically significant effect on risk of non-CHD death Richard Peto, University of Oxford, personal communication, In the trials shown in Tablenone of the percentage differences in risk of non-CHD death or total mortality was statistically significant except for the WHO Clofibrate Trial.
In the final mortality follow-up, however, the Committee of Principal Investigators of that study found that the excess mortality in the clofibrate-treated group did not continue after the end of treatment, and they could not find a reasonable explanation for the excess mortality that did occur during the period of active treatment.
The excess deaths were due to a variety of non-CHD causes and had no apparent association either with the extent of reduction in TC or with duration of treatment with clofibrate. These results do not rule out the possibility of a toxic effect, but seem more consistent with the hypothesis that the excess of deaths in the treated group was the result of random sampling variation.
The possible adverse effects of the drugs used in these trials are not strictly relevant to a report on diet and health and are not discussed further. The safety of dietary changes to lower serum TC is discussed in Chapter 28 of this report. There is no firm evidence to indicate that any of the dietary interventions used in the trials described above increased the risk of non-CHD deaths.