For the past few years nutritionist and epidemiologist have been having trouble demonstrating that dietary saturated fats and cholesterol increase the risk of coronary heart disease (CHD). However they kept their noses to the grind stone and have settled on trans fats as the culprit. Trans fats are semi-solid fats which result from the conversion of liquid oils into their partially hydrogenated forms. They are present in most of the good things you eat, everything from donuts to milk. The Food and Drug Administration has gone along with this most recent fat fad and decided that food labels must state the amount of trans fats in all products. The Department of Agriculture has made a key recommendation that trans fat intake should be limited in their new food pyramid guidelines. Several other actions have been taken by various governmental agencies at home and abroad to limit or eliminate trans fats from our diets.
My question is: are trans fats all that bad and is worth the time, money and trouble to take them out of foods. I seem to remember when these same agencies were trying to limit saturated fat and cholesterol in our diets. Actually they still are because they are not able to face the facts that dietary saturated fat and cholesterol do not increase risk of heart disease.
REVIEW OF THE DATA ON DIETARY FATS AND HEART DISEASE
The more important papers in the past 10 years concerned the supposed dangers of trans fats can be found in a review article written by Mozaffarian et al (1). It was important because it was picked up by the news media and given the appropriate level of hype. But, as I have asked before, did anyone in the news media or anywhere else actually read this paper? Well I did and here is my summary of it and the studies it uses to suggest that trans fats are bad. I will also review a couple of others along the way.
For each of the studies I will provide a brief summary for the readers who doesn’t want to cloud their mind with all of the statistical based arguments.
BREIF SUMMARIES OF EACH OF THE STUDIES
Study 1. Mozaffarian et al (1).
The data in this review article clearly shows no association between dietary saturated fat or cholesterol and the incidence of heart disease. They also provide data which indicates a slight increase in risk of heart disease ( relative risk: 40%, actual risk: 0.12%). This very low increase becomes insignificant when amount of fiber in the diet is taken into account. It seems that people who eat the most trans fats also have the lowest quantity of fiber in their diets. This is obviously related to the attitude: that French fries are better than broccoli any day. So it’s the lack of fiber that is dangerous, not the intake of trans fats.
Study 2. Nurse’s Health Study by Oh et et al (4).
These authors demonstrate in agreement with other studies that dietary total fat, saturated fat and unsaturated fat do not increase the risk of heart disease; however, they do try to implicate trans fat. Their story is poor because the data on estimated risks are only slightly different from no effect. There is no indication that they corrected the data for fiber intake which would reduce any elevated risk even more, so my judgment is the data are too weak to show any actual differences.
Study 3. Zutphen Elderly Study by Oomen et al (5).
Another study which shows a marginal increased risk of heart disease associated with dietary trans fat intake. Too little data and too close to call.
4. The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study by Pietinen et al (6).
One more study which shows no increased risk of heart disease associated with dietary saturated fat, cholesterol, monounsaturated fats, total triglycerides and saturated fatty acids. Dietary trans fat was not associated with an increase in heart disease but it was associated with marginally with increased risk of death due to heart disease. The numbers involved in this portion of the study are very low and the actual increased risk is also very small (0.12%) I don’t believe there is anything to worry about.
MORE DETAILED ACCOUNT
Because this subject is so important and it has insinuated itself into brains of so many scientists, physicians, news media reporters and the public in general, I believe a detailed account of the problems with these studies should be provided. Hence, the following.
In their review Mozaffarian et al (1) present a summary table which shows the relative risk (RR) and the 95% confidence intervals (CI) found in four prospective cohort studies. As usual I will present the data from each of the studies in the review and evaluate the authors risk estimates by making graphs using their data.
Study 1. Ascherio et al (2)
One of these studies which is often quoted as demonstrating that trans fat intake is linked to elevated risk of heart disease was published by Ascherio et al.(2). This is an important paper in many ways because it also presents data that shows no increased risk in the incidence of heart disease due to intake of saturated fat or cholesterol. Hasn’t been too long ago that every one believed they were dangerous dietary bad actors. Many people still do and this is partly due to the failure of the governmental agencies and news media to inform the general public of this change in belief.
In Ascherio et al (2) people were categorized according to the intake of the various kinds of fat (grams/day) and the incidences of heart attack (myocardial infarct, MI) were recorded (Figure 1).
Figure 1. The relative risk (RR) of myocardial infarct (MI) as a function of the intake of saturated fat or cholesterol. The data points show the RR plus and minus the 95% confidence intervals. The intake categories are shown on the X axis and reflect the amount of each fat in grams/day. The lowest amount is 1 and the highest is 5. The dashed line represents the no effect level of 1.0.
It is clear that intake of saturated fat or cholesterol is not related to any increase risk of MI. This conclusion has been confirmed in several more studies some of which are discussed in the following sections.
In this same study the authors examined for any relationship that might exist between trans fat and the risk of heart disease. Their data are shown in Figure 2. There is no significant increase in myocardial infarction (MI) in the 2 - 4 categories which represent from 2.2 to 3.3 grams/day of trans fat. The intake in category 1 was 1.5 gm/day. The only statistically significant group was the people who consumed 4.3 gm/day (category 5). So my conclusion from these data would be that a very weak suggestion of an increase risk of MI was found in group 5. By “weak suggestion” I mean barely statically significant and may not be real.
When the authors adjusted their data for fiber intake there was no hint of and increase in risk due to trans fat intake. It has been suggested that increased dietary fiber intake significantly reduces heart disease (3). The correction for fiber intake is based on the data that show people who consume a fatty diet also consume less fiber. Since fiber is presumed to be protective against MI the incidence increases when dietary fiber intake is low (3). I am not sure we can believe this any more than anything else in these papers. One conclusion you could draw from these data is trans fat is not the problem and it may be the lack of fiber.
Figure 2 The relative risk (RR) of myocardial infarct (MI) without (A) and with (B) correction for dietary fiber intake. The RR plus and minus the 95% confidence intervals are shown as a function of amount of dietary trans fat The intake categories are shown on the X axis and reflect the amount of each trans fat in grams/day. The lowest amount is 1 and the highest is 5.
Adding to my lack of enthusiasm concerning any elevated risk of MI due to dietary intake of trans fats is the following incidence data shown in Figure 3. As you can see the incidence of MI in the three fat groups appear to be almost identical. This makes it very difficult to accept that any significance can be granted to trans fat group and not to the other groups. In most of these kinds of papers the incidence data are not shown. I believe you can guess the reason.
From these data in Figure 3 the actual risks can be calculated. I will do this for trans fat only, the others are similar. The authors calculate a RR of 1.40 with a 95% CI (1.1 -1.79) and would say there is a 40% increase in the risk of MI due to trans fat intake. Note that the lower value for CI is 0.1 away from non-significant. It gets worse, when you calculate the actual increase which is 0.12%. So even if the actual risk were significant the odds of adverse effects from consuming trans fats are small indeed.
Figure 3. Incidence of myocardial infarct as function of dietary fat. Percent incidence calculated from the raw data in Ascherio et al (1). Fat intake categories are the same as in Figure 2 above.
FATAL CORONARY DISEASE
Ascherio et al (1) also examined the risks of fatal heart disease and dietary fat. The number of people who died in these studies was very small which makes any conclusion concerning these data very suspect. The RR’s for increased death rate in the saturated fat group were not significant except in the highest intake category (RR = 2.21 95% CI, 1.38 - 3.54, see Figure 4 A). The actual increased risks is 0.08%. The amount of cholesterol in the diet did not have any significant effect on the risk of death due to CHD (Fig 4 B).
Figure 4. The relative risk of death due to CHD in relation to saturated fat (A) and cholesterol (B)
Trans fat appeared to elevate the risks of death (Fig 5 A); however, when these data were corrected for fiber intake the risks became non-significant (Fig. 5 B). The actual difference in risks between the lowest intake category (0.07%) and the highest (0.12%) was 0.05%. These very small numbers add to the doubt that an statistical significance can be ascribed to these data.
As indicated previously, if any significant increase in the risk of CHD in people who consume a lot of trans fat it is not due to the fat, but the lack of fiber. So don’t blame the fat, blame the lack of fiber
Figure 5 The relative risk of death due to dietary intake of trans fats. The multivariate adjusted relative risks are shown in A and these risks corrected for fiber intake are shown in B.
Study 2 Nurse’s Health Study (NHS) by Oh et al (4).
In this paper women were studied for 20 years and the incidence of heart disease and dietary fat intake were compared. The NHS data are important because they show no increase in risk for the following forms of fat:
· Total fat,
· Saturated fat,
· Mono-unsaturated fat
· Poly-unsaturated fat.
These studies are exemplified by Figure 6 A which shows that dietary saturated fat intake does not increase the risk of coronary heart disease (CHD). Dietary intake of poly unsaturated fat appears to result in a reduced risk of CHD (Figure 6 B). Once again the data are weak and with only one RR (category 5) showing any significant decrease. It is difficult to say with any confidence that the risks of CHD are reduced by eating poly unsaturated fats.
Figure 6 Relative risk of coronary heart disease and dietary intake of saturated and poly unsaturated fat. The energy intake categories represent the percent of energy derived from the specific fat in question. Category 1 being the lowest and 5 the highest.
The results for trans fat study are weak in the opposite direction (Figure 7). That is, they show and upward trend and thus hint at an increased risk of CHD due to dietary trans fat but once again the data in support of this are weak. In category 2 the RR is clearly not significantly different from the no effect line of 1.0. However the level for category 3 is elevated above the no effect line. But, then the RR for category 4 decreases and is not elevated significantly above 1.0. In the final category (5) the RR of 1.33 is elevated but the 95% CI (1.07 -1.66) just barely misses crossing 1.0. No data are provided on the incidence of CHD in each category so I was not able to draw a graph of these data as I did in Figure 3 above. The RR of 1.33 is the one published in the review by Mozaffarian et al (1), and no mention is made of the tenuous nature of its information or that decrease intake of fiber was taken into account.
Figure 7. Relative risk of coronary heart disease and dietary intake of trans fat. The energy intake categories are explained in caption of figure 4.
Study 3. Zutphen Elderly Study by Oomen et al (5). Written for the scientist.
In this study older men (age 64-84) were studied for 10 years and their trans fat intake was correlated with risk of CHD. The authors concluded that there was an increase in CHD with a 2% increase in dietary trans fat. This was based on a RR of 1.28 and (95% CI of 1.01 – 1.61). This looks like another barely significant RR and I advise waiting until the data form next years’ study is available before you make up your mind. No data on incidence or relative risk as a function of fat intake were given in this paper; therefore , it is difficult to judge it’s value.
Study 4. The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study by Pietinen et al (6).
This is an important study because the authors conclude that risks of CHD are not associated with dietary intake of the following nutrients:
· Saturated fat
· Cholesterol
· Cis-monounsaturated fats
· Total triglycerides,
· Saturated fatty acids
· C12 – C16 Saturated fatty acids.
These authors also report that linoleic and linlenic acids are not associated with increase or decrease risk of CHD. These findings concerning linoleic and linolenic acid are in contradiction to some of the more recent studies which have claimed these two fatty acids decrease the risks of CHD (4).
In their analysis of trans fat they did not show any significant increase in the risk of non-fatal CHD; however they claim that fatal CHD is increased by trans fat intake. Figure 8 shows that the only RR of significance is for the highest intake category ( RR 1.39 95% CI 1.09-1.76). In light of the up and down nature of the preceding values, none of which come close to being statistically significant, it is likely that 1.39 is also not significant. If a correction for fiber intake had been used it probably would not be significant. The actual increase risk in this case is only 0.16% compared to the 39% relative risk.
Figure 8. Relative risk of fatal CHD and dietary intake of trans fats. Data taken from Pietinen et al (6).
Retrospective case-control studies
The remaining studies included in the review by Mozaffarian et al (1) were retrospective case-control studies which have smaller numbers of individuals involved and are less likely to be valid.
In the first study the content of fatty acids in adipose tissue was examined in 671 men in 8 European countries and Israel with acute myocardial infarction (7). The odds ratio was 0.97 (95% CI 0.56-1.67) and obviously not statistically significant. So, no evidence for an increase in the risks of CHD due to fatty acids was found.
The second study also examined the content of fatty acids in adipose tissue but this time in Costa Rica (8). They examined their data by adjusting the values according to the following scheme. First they adjusted the data for income, history of diabetes , history of hypertension, physical activity , smoking, years living in the house and alcohol intake (Figure 9 A). As you can see, this adjustment made the odds ratios increase but not significantly (Fig 9 B). So they tried further adjustments for adipose tissue, linolenic acid and intake of vitamin E, saturated fat and total energy. These adjustments finally gave the authors a statistically significant increase in the odds ratio in group 5 of OR 2.94 (95% CI 1.36-6.37); Figure 9 C. This is the value in table 2 of the review by Mozaffarian et al (1). No mention of the non-significant odds ratios in the first two adjustments. The possibilities for errors in a study containing so many adjustments, some valid and some may be not, make the final odds ratio very suspect and not credible.
Figure 9. Odds ratios and risk of myocardial infarction as a function of the amount of trans fatty acid in adipose tissue. All data taken form table 3 in Baylin et al (8).
The last study listed in the review is an Australian study which involved 209 cases of myocardial infarction (9). The relative risk of MI in the highest category of dietary intake was 2.25 (95% CI 1.16-4.32), and this value was published in Figure 4 in the review by Mozaffarian et al (1). I have plotted the RRs for each intake category in Figure 10 A below and it is obvious the only the last RR is statistically significant. However, this increase in risk was due to decline in the number of people in the control group (see Figure 10 B) which was accompanied by a similar increase in the number of cases of MI. The true RR would have been considerablely lower if the number in the control group had not taken a sudden an unexplained drop.
Figure 10. Dietary intake of trans fat and first myocardial infarct (MI). These data taken from table in Clifton et al (9).
SUMMAR OF REVIEWED STUDIES
Evidence that trans fatty acids in the diet elevate the risk of CHD is very weak and if the lack of fiber in the diet is taken into consideration there is no significant increased risk of CHD due to dietary trans fat.
These studies demonstrate that the following fats do not increase the risk of CHD:
· Total fat,
· Saturated fat,
· Cholesterol
· Mono-unsaturated fat
· Poly-unsaturated fat
· Cis-monounsaturated fats
· Total triglycerides,
· C12 – C16 Saturated fatty acids.
STUDIES NOT COVERED IN THE MOZAFFARIAN REVIEW
Some important studies which were not included in the Mozaffarian review (1) will be discussed in this section.
For historical and prophetic reasons the study by Micheal DeBakey’s group published in 1964 should be mentioned (10). They analyzed serum cholesterol values in 1700 patients and found no correlation between cholesterol and atherosclerotic disease. Apparently no one listened and cholesterol was declared the enemy. The battle went on for years, but as you can see from the review of the preceding paper and by ref 11 below, cholesterol has be exonerated by many people.
A large prospective study involving 80,082 women 34 to 59 years of age seems important not only because of its size but for the many different fats studied (11). They found no increase risk of CHD as a result of the following dietary fats:
· Total fat
· Animal fat
· Vegetable fat
· Saturated fat
· Mono-unsaturated fat
· Poly-unsaturated fat
· Cholesterol
The only item on their study menu which showed even the slightest increased risk was trans fat and then only in the highest intake category (Figure 11). It is hard to believe that the RR for this group 1.27 (95% CI 1.03-1.56) is of any significance since the amount of trans fat intake in category 5 differs from category 4 by only 0.05%. This is very weak data point and lacks credibility. No numbers of individuals were given in this paper so the actual risks could not be calculated.
Figure 11. Relative risk of CHD as function of trans fat intake. Data from table 3 in Hu et al (11
In a follow-up study these authors say that diet high in fat and low in carbohydrates is not associated with increased risk of heart disease (12). They seemed surprised by their findings. Maybe they should read their own paper.
SUMMARY
Although dietary cholesterol was declared the enemy years ago, the signs that this was not true were provided by none other than Micheal Debakey back in 1964 (10). He has since been proven to be correct. The other highly touted villains in our diet like total saturated fat and animal fat have also bitten the dust. The latest epidemiologist’s horse by the name of trans fats appears to be stumbling and may fall in the future. I believe it has already fallen judging by the marginal data which is said to support its dangers.
REFERENCES
1. Mozaffarian et al 2006 Trans fatty acids and cardiovascular disease. NEJM 354:1601-1613.
2. Ascherio A, Rimm EB, Giovannucci EL, et al. Dietary fat and risk of coronary heart disease in men: cohort follow up study in the United States. BMJ 1996;313:84–90.
3. Rimm EB, Ascherio A, Giovannucci E, Spiegelman D, Stampfer MJ, Willett WC 1996 Vegetable, fruit and cereal fiber intake and risk of coronary heart disease among men. JAMA 275:447-51.
4. Oh K, Hu fB, mason JE, Stampfer MJ Willett WC 2005 Dietary fat intake and risk of coronary heart disease in women: 20 years of follow-up of the Nurses’ Health Study. Am J Epidemiol 161:672-679.
5. Oomen CM, Ocke MC, Feskens EJ, et al. Association between trans fatty acid intake and 10-year risk of coronary heart disease in the Zutphen Elderly Study: a prospective population-based study. Lancet 2001;357:746–51.
6. Pietinen P, Ascherio A, Korhonen P, et al. Intake of fatty acids and risk of coronary heart disease in a cohort of Finnish men: The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Am J Epidemiol 1997;145:876–87.
7. Aro et al 1995 Adipose tissue isomeric trans fatty acids and risk of myocardial infarction in nine countries: the EURAMIC study. Lancet 345:273-278.
8. Baylin A et al 2003 High 18:2 trans-fatty acids in adipose tissue are associated with increased risk of nonfatal acute myocardial infarction in Costa Rican Adults, J Nutr 133:1186-1191.
9. Clifton PM, Keogh JB , Noakes M 2004 Trans fatty acids in adipose tissue and the food supply are associated with myocardidal infarction. J Nutr. 134:874-879.
10. Garrett HE, Horning EC, Creech BG, Debakey M 1964 Serum cholesterol values in patients treated surgically for atherosclerosis. JAMA 189:655-659.
11. Hu FB et al 1997 Dietary fat intakes and the risk of coronary heart disease in women. N Engl J Med 337:1491-1499
12. Halton TL et al 2006 Low-carbohydrate-diet score and the risk of coronary heart disease in women. N Engl J Med 355:1991-2002.
This is really a long post. Now are you saying fat isn't too bad, or doesn't cause heart problems?
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