Trans Fatty Acids and Coronary Heart Disease

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Trans Fatty Acids and Coronary Heart Disease

The New England Journal of Medicine -- June 24, 1999 -- Vol. 340,

No. 25

 

 

Trans-unsaturated fatty acids are produced commercially in large

quantities by heating vegetable oils in the presence of metal

catalysts and hydrogen to form shortening and margarine.

 

They are so named because the carbon atoms adjacent to their double

bonds are on opposite sides, resulting in a straight configuration

and a solid state at room temperature.

 

In contrast, naturally occurring unsaturated fatty acids contain

double

bonds as cis isomers, with adjacent carbons on the same side of the

double bond, resulting in a bent shape and a liquid state at room

temperature.

 

Partial hydrogenation, the process used to create trans fatty acids,

is primarily used to produce solid fats.

 

However, it also removes essential polyunsaturated fatty acids, such

as linolenic acid and linoleic acid, because they tend to oxidize,

causing the fat to become rancid with prolonged storage or when

exposed to the high temperatures used for commercial deep-fat

frying.

 

Production of partially hydrogenated fats began early in the 20th

century and increased steadily until about the 1960s, as " processed

vegetable fats " displaced animal fats in the diets of most people in

industrialized countries.

 

The initial motivation was lower cost, but health benefits were

later purported. The average per capita consumption of trans fatty

acids from partially hydrogenated oils has remained at about 2

percent of calories

since the 1960s, because of the increased use of these fats in

commercially baked products and fast foods.

 

By the early 1990s it became apparent that the consumption of trans

fatty acids had uniquely adverse effects on blood lipid levels in

metabolic studies and was associated with an increased risk of

coronary

heart disease in epidemiologic investigations.

 

A 1995 industry-sponsored review concluded that there was

insufficient

evidence to take action and that further research was needed.

Since then many more metabolic and epidemiologic studies have

confirmed

the " adverse " effects of trans fatty acids, stimulating the Food and

Drug Administration to announce plans to include the trans-fatty-

acid content of foods on product labels.

 

In this article we shall review the effects of trans fatty acids on

blood lipid levels that have been identified in metabolic studies

and

the associated risk of coronary heart disease that has been

identified in epidemiologic studies.

 

 

Metabolic Studies

 

Early metabolic studies generally found that the cholesterol-raising

effect of hydrogenated fat was less than that of saturated fats.

 

However, the focus on total lipid levels masked the fact that

although

trans fatty acids and saturated fatty acids increase low-density

lipoprotein (LDL) cholesterol levels to a similar degree, trans-

fatty

acids also lower beneficial high-density lipoprotein (HDL) levels as well.

 

A 1990 study demonstrated that the replacement of a diet high

in " oleic " acid (10 percent of the daily energy intake), the primary

monounsaturated fat in diets,

with a diet high in trans fatty acids increased LDL cholesterol

levels by 14 mg per deciliter (0.37 mmol per liter) and decreased HDL

cholesterol levels by 7 mg per deciliter (0.17 mmol per liter).

 

As a result, the ratio of LDL cholesterol to HDL cholesterol was

significantly higher with the trans-fatty-acid diet (2.5 than with the

oleic-acid diet (2.02).

 

These findings have been confirmed in many studies, including the

study

by Lichtenstein et al. reported in this issue of the Journal, with

the use of various levels and mixtures of trans fatty acids.

 

summarizes the randomized trials that directly compared the effects

of

trans fatty acids with those of isocaloric amounts of cis fatty

acids.

 

 

Because trans fatty acids increase LDL cholesterol to levels similar

to

those produced by saturated fatty acids and also decrease HDL

cholesterol levels, the net effect of trans fatty acids on the ratio

of LDL to HDL is approximately double that of

saturated fatty acids.

 

The only somewhat discordant result was from a small Malaysian

study, which found a considerably stronger adverse effect of trans fatty acids;

we have conservatively excluded this result in estimating the

regression line.

 

We also did not include the study by Almendingen et al. in because

they did not compare a diet high in trans fatty acids with a diet high in oleic

acid or polyunsaturated fat.

 

The effect of trans fatty acids on the ratio of LDL cholesterol to

HDL was significantly larger than that of saturated fatty

acids in each of the six studies that allowed a direct comparison.

 

Collectively, these studies provide definitive evidence that trans

fatty acids raise this ratio more than do saturated fatty acids.

 

As shown by the best-fit regression line in , an absolute increase

of 2 percent in the intake of trans fatty acids would raise the ratio of LDL

cholesterol to HDL cholesterol by 0.1 unit.

 

Since a 1-unit increase in the ratio is associated with a 53 percent

increase in the risk of coronary heart disease, the average intake

of 2 percent of calories from trans fatty acids in the United States

would be predicted to account for a substantial number of deaths from coronary

heart disease.

 

Other trials have compared the effects of butter and margarine on

blood lipid levels.

 

A meta-analysis of these investigations, however, showed that butter

and margarines, which typically contain 20 to 25 percent trans fatty

acids, have similar effects on the ratio of total cholesterol to HDL

cholesterol.

 

These results confirm the deleterious effects of trans fatty acids

on blood lipid levels and indicate that these may offset the beneficial effects

of polyunsaturated fat.

 

Besides increasing the ratio of LDL cholesterol to HDL cholesterol,

trans fatty acids increase Lp(a) lipoprotein levels when they are

substituted for saturated fatty acids.

 

A significant increase in Lp (a) lipoprotein levels was reported in

9 of 10 trials, with an average increase of 0.5 mg per deciliter per 2

percent of energy intake from trans fatty acids.

 

Trans fatty acids also raise triglyceride levels measured while

subjects are fasting.

 

Numerous studies have reported increases in triglyceride levels

ranging from 1.0 to 24 mg per deciliter (0.01 to 0.27 mmol per liter), with

an average increase of 3.0 mg per deciliter (0.03 mmol per liter) per 2 percent

of energy intake from trans fatty acids.The effect of such

an increase on the risk of cardiovascular disease, is unfavorable.

 

 

Epidemiologic Studies

 

The strong correlation between the level of intake of saturated

fatty acids and the rates of coronary heart disease among the 16

populations examined in the Seven Countries Study is often quoted as evidence

that the consumption of saturated fat increases the risk of coronary

heart disease.

 

A subsequent biochemical analysis of food composites representing

the average intake of each cohort at base line not only confirmed that the

intake of saturated fatty acids was strongly correlated with the risk of

death from coronary heart disease (r=0.88, P<0.001) but also showed

that the intake of trans fatty acids was correlated with the risk of

death from coronary heart disease (r=0.78, P<0.001).

 

Several case-control or cross-sectional studies have also been

conducted. In a case-control study of subjects in the Boston area,

we

found a strong and significant positive association between the

intake of trans fatty acids, assessed with the use of dietary

questionnaires, and the risk of acute myocardial infarction.

 

The relative risk of acute myocardial infarction for the quintile

with the highest intake of trans fatty acids as compared with the

quintile with the lowest intake was 2.4 (P for trend <0.001); this

association was entirely explained by the intake of these fats from hydrogenated

vegetable oil (margarine).

 

Bolton-Smith et al. performed a cross-sectional analysis of the

association between the intake of trans fatty acids and the presence

of previously undiagnosed coronary heart disease among participants in

the Scottish Heart Study.

 

The intake of trans fatty acids was positively correlated with the

ratio of LDL plus very-low-density lipoprotein cholesterol to HDL

cholesterol.

 

The odd ratios for coronary heart disease in the quintile with the

highest intake as compared with the quintile with the lowest intake

were elevated but not significantly so (1.26 in women and 1.08 in men).

 

The strongest epidemiologic evidence relating dietary factors to the

risk of coronary heart disease has been provided by three large

prospective studies: the Health Professionals Follow-up Study, the

Alpha-Tocopherol Beta-Carotene Cancer Prevention Study, and the

Nurses' Health Study.

 

Those studies assessed the intake of trans fatty acids using

detailed food-frequency questionnaires whose results were validated by

comparison with the composition of adipose tissue or food diaries.

 

Each of these studies reported an adverse effect of trans fatty

acids. The relative risk of coronary heart disease associated with an absolute

ncrease of 2 percent in the intake of trans fatty acids was 1.36

(95 percent confidence interval, 1.03 to 1.81) in the Health

Professionals Follow-up Study, 1.14 (95 percent confidence interval, 0.96 to

1.35) in the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study, and 1.93

(95 percent confidence interval, 1.43 to 2.61) in the Nurses' Health

Study.

 

The higher relative risk in the Nurses' Health Study may have

resulted from the fact that there were four dietary measurements during the

follow-up period, thereby reducing the degree of error in assessing

trans-fatty-acid consumption.

 

In these three cohorts, the relative risks were higher than those

for saturated-fat consumption. For example, in the Nurses' Health Study,

replacing 5 percent of energy intake from saturated fat with

unsaturated

fat was associated with a 42 percent decrease in the risk of

coronary

heart disease, whereas replacing 2 percent of energy intake from

trans fatty acids with cis fatty acids was associated with a 53 percent decrease

in the risk.

 

These studies have been criticized on the grounds that measurements

of the intake of trans fatty acids were unreliable however, random

errors

in measuring the intake would only have led to an underestimation of

the association with the risk of coronary heart disease.

 

It has also been suggested that the observed associations resulted

from a shift from the use of butter to the use of margarine among high-risk

subjects. If so, the association between the intake of trans fatty acids and

the risk of coronary heart disease should have been weaker among

subjects with margarine consumption and stronger during the first few years of

follow-up.

 

However, in the Nurses' Health Study,) the exclusion of women who

changed their diet before the beginning of the study strengthened

the association.

Moreover, consumption of foods high in trans fatty acids such as

cookies, which are hardly perceived as healthy, was also positively

associated with the risk of coronary heart disease.

 

Confounding as a result of unmeasured or poorly measured risk

factors is a potential problem in any observational study, but these

associations

were adjusted for many risk factors related to diet and lifestyle,

and no credible confounding factor has been identified.

 

Adjustment for the intake of dietary fiber attenuated the relation

of trans-fatty-acid intake to the risk of coronary heart disease in the Health

Professionals Follow-up Study, but not in the other two

studies (and Hu FB: personal communication).

 

Thus, prospective studies provide consistent evidence that the

consumption of trans fatty acids increases the risk of coronary

heart disease.

The observed relative risks of coronary heart disease were larger

than one might predict from the effects of trans fatty acids on LDL and

HDL cholesterol levels alone.

 

The increases in triglyceride and Lp(a) lipoprotein levels account

for only a small increase in risk; therefore, other mechanisms may be involved.

 

Conclusions

 

Metabolic and epidemiologic studies indicate an adverse

effect of trans fatty acids on the risk of coronary heart disease.

 

Furthermore, on a per-gram basis, the adverse effect of trans fatty

acids appears to be stronger than that of saturated fatty acids.

 

When ingredients with no known nutritional benefit are added to

foods, a low threshold for evidence of harm should be adopted, and it should be

the responsibility of food manufacturers to show that their products

are safe.

 

In Europe, producers have responded rapidly by developing products

free of trans fatty acids that are also low in saturated fats.

These products are also becoming available in the United States, but

heavily hydrogenated margarines still retain a large share of

the market.

 

In the United States,25 percent to 37 percent of the intake of

trans fatty acids from hydrogenated vegetable oil comes from

margarines; the remainder comes from baked goods, fried fast foods, and other

prepared foods.

 

Current U.S. regulations provide an incentive to manufacturers to

produce foods high in trans fatty acids because food labels are not

required to include the amount of trans fatty acids.

 

Many scientists agree that the amount of trans fatty acids should be

stated on food labels. One simple option is to combine this

information with the saturated-fat content.

 

This approach, however, ignores the observation that the intake of

trans fatty acids is associated with a higher risk of coronary heart

disease

than is the intake of saturated fatty acids.

 

Although changes in labeling are important, they are not enough.

Many fast foods contain high levels of trans fatty acids, are exempt

from labeling regulations, and can even be advertised as

cholesterol-free and cooked in vegetable oil.

 

For example, the consumption of one doughnut at breakfast (3.2 g of

trans fatty acids) and a large order of french fries at lunch (6.8 g

of trans fatty acids)

adds 10 g of trans fatty acids to one's diet and represents 5

percent of the total energy intake on an 1800-calorie diet -- and neither

product needs to be labeled.

 

Five years ago, it became evident that consumption of trans fatty

acids

adversely affects blood lipid levels.

Subsequent studies have confirmed these metabolic findings and

strengthened epidemiologic evidence of an important increase in the

risk

of coronary heart disease with the consumption of trans fatty acids.

 

These data highlight the need for labeling requirements that include

fast foods.

 

Given the proper incentives, the food industry could replace a large

proportion of the partially hydrogenated fats used in foods and food

preparation with unhydrogenated oils.

 

Such a change would substantially reduce the risk of coronary heart

disease at a moderate cost, without requiring major efforts focused

on

education and behavioral modification.

 

 

Alberto Ascherio, M.D., Dr.P.H. Harvard School of Public Health

Boston,

MA 02115

 

Martijn B. Katan, Ph.D. Peter L. Zock, Ph.D. Wageningen Center for

Food

Sciences 6703 HD Wageningen, the Netherlands

 

Meir J. Stampfer, M.D., Dr.P.H. Walter C. Willett, M.D., Dr.P.H.

Harvard

School of Public Health Boston, MA 02115

 

Address reprint requests to Dr. Ascherio at the Department of

Nutrition,

Harvard School of Public Health, 665 Huntington Ave., Boston, MA

02115,

or at alber-.

 

We are indebted to Jill Arnold for her expert assistance with the

manuscript.

--------------------------------

Posted:

Sat Oct 02, 2004 1:28 pm

Post subject: Harvard Review: Trans-fats & Heart Disease

--

 

Harvard Review: Trans-fats & Heart Disease

 

Harvard Review of evidence verifies that eating " trans-fats "

increases

risk of Heart Disease

 

http://www.udoerasmus.com/articles/reviews/item4.htm

 

Boston, MA -- Over the course of the last decade, numerous studies

have

examined the relationship between the consumption of trans fatty

acids

found in partially " hydrogenated " oils and coronary heart disease

(CHD).

 

 

A comprehensive review of the scientific evidence confirms that

eating

trans fatty acids increases the risk of CHD.

 

The review, published in the June 24, 1999, New England Journal of

Medicine, is authored by researchers at the Harvard School of Public

Health and the Wageningen Centre for Food Sciences in the

Netherlands.

 

Lead author, Alberto Ascherio, said " Coronary heart disease kills

500,000 Americans each year.

 

According to our estimations, if trans fats were replaced by

'monounsaturated' oils, we would expect to see at least 30,000 fewer

persons die prematurely from CHD each year. "

 

Trans fatty acids are found in most margarines, in many commercially

baked goods, and in the fats used for deep-frying in many

restaurants.

 

The commercial advantages trans-fats hold over monounsaturated oils

is

that they are solid at room temperature, they can remain on the

shelf

for a longer time before becoming rancid, and they allow for deep-

frying

at higher temperatures.

 

" Because of concerns that trans fatty acids increase risk of CHD, "

said

Ascherio. " The Food and Drug Administration is considering new

regulations for nutrition labels that will require manufacturers to

report the amount of trans fatty acids. "

--------------------------------

 

Under current guidelines, a consumer who is trying to be heart-

healthy

might choose a product that is labeled as being low in 'cholesterol'

and

saturated fat, but which is high in harmful " trans- fats " .

 

The researchers reviewed more than 25 metabolic and epidemiological

studies.

The metabolic studies showed that trans-fats have a two-pronged

harmful effect on blood cholesterol levels:

 

trans fats increase " low-density " lipoprotein cholesterol (LDL-- " bad

cholesterol " ) and decrease " high-density " lipoprotein cholesterol

(HDL-- " good cholesterol " ).

 

The epidemiological studies tracked people's eating habits and

examined

occurrence of CHD later in their lives.

 

These studies found a link between consumption of trans fats and CHD

that was higher than expected from the results of the metabolic

studies.

 

 

" We don't fully understand all of the ways that trans fats increase

risk

of CHD, " said Ascherio, " but it seems clear that they do increase

risk. "

 

 

Ascherio and colleagues urge the food industry to replace the

partially

hydrogenated fats used in foods and in food preparation with

unhydrogenated oils:

 

" Such a change would substantially reduce the risk of coronary heart

disease at a modest cost. "

 

Alberto Ascherio is an associate professor of nutrition and

epidemiology

at the Harvard School of Public Health.

 

See also: Trans Fatty Acids and Coronary Heart Disease, The New

England

Journal of Medicine -- June 24, 1999 -- Vol. 340, No. 25.

 

For further information, please contact:

 

Bob Brustman

Harvard School of Public Health

Department of Nutrition

665 Huntington Avenue

Boston, MA 02115

 

Phone: 617-432-3952

Email: bru- ;

------------------------------

 

Trans- fat lawsuit May 15, 2003

UPDATED PRESS RELEASE FROM STEPHEN JOSEPH

OF BANTRANSFATS.COM

 

I am pleased to announce that we are voluntarily dismissing the Oreo

lawsuit. The factual and legal basis for the lawsuit when it was

filed

was that the American people did not know about trans fat. At best,

perhaps 10-15 percent knew. The American people were being kept in

the

dark by the food manufacturers. The word " trans fat " is not even on

food

labels. That was then. This is now.

 

After three days of incredible national publicity, everyone in

America

knows about trans fats, and if anybody doesn't, I don't know where

on

earth they've been hiding. The factual and legal basis for the

lawsuit

has totally disappeared. I certainly could not tell a court now that

nobody knows about trans fat.

 

Here is an e-mail that I received from a lady that made me realize

that

the lawsuit had been successful, and that it was no longer

necessary:

 

" You have me reading labels! I picked up only two out of many boxes

of

children's cereal's yesterday in the grocery store, and two of them

contained partially hydrogenated soybean oil – also saw it in Cool

Whip

and Nestles instant hot chocolate. My God there's a monster out

there.

My husband came home with a package of Chips Ahoy " Light " cookies,

and I

grabbed them and read the label. You guessed it – they have

partially

hydrorogenated oils! "

 

Did that lady have a right to know? Or would you have preferred

Kraft

and the other food manufacturers to have kept her totally in the

dark?

Here's another one:

 

" I was unaware of trans fats myself. I have always been a label

reader

but never knew to look for hydrogenated oils as a substance to

avoid. It

is scary to think how long I have been consuming trans fat against

my

will. "

 

And another from a young girl:

 

" My name is -------. I read about trans fats on msn today. I thank

you

for warning me about them. I love Oreos but I see your point. They

should cut out trans fat. I may be only fourteen but I feel I can

make a

difference by telling people in the small town I live in about trans

fats. I never have heard of them until today, May 14, 2003. I wish

you

good luck on your law suit and see your purpose. I really don't have

time for a phone call but I check my email a lot, my email address

is

-----------. Thank you, and Good Luck!!! "

 

I have received thousands of similar e-mails.

 

It is just great that Kraft has now announced in response to the

lawsuit

that it is " actively exploring ways to reduce trans fats in Oreo. "

Kraft

is accepting that there is a problem that must be solved. Good.

Hopefully, we will see a trans fat-free version of the Oreo soon, so

that those of us who love Oreos (I really do) don't have to eat

unsafe

trans fats to enjoy them. We have that right, don't we? Kraft should

give us all a choice.

 

It's now up to each food manufacturer to decide how to respond to

the

new public awareness of the existence and danger of trans fats.

Let's

hope that they respond responsibly.

 

No money was ever requested in the lawsuit. There is no greed

factor. No

one has made a penny out of it. And it did not cost one penny of

taxpayers' money.

 

Incidentally, I am generally against lawsuits against food

manufacturers, and I am certainly against the MacDonald's case which

I

think is totally ridiculous. I've said that over and over again this

week. Everyone knows that fast food is unhealthy and they have to be

responsible for their own actions.

 

Trans fat was a unique situation, because so few people knew about

it,

it isn't on the label, Kraft was opposing trans fat labeling saying

it

would be " confusing, " and the FDA says that we should eat none of

it.

 

There should be no more trans fat lawsuits, because everyone now

knows

about it, and if anyone files one they should consider me to be an

opponent. The existence and danger of trans fats is now common

knowledge

as a result of the last three days of publicity and as far as I am

concerned there is no longer any basis for suing anyone.

 

And to those of you who thought I was infringing your freedom,

remember,

when the facts are suppressed you have no freedom. You had a right

to

know about trans fats, and now you do.

 

What you do with the information is entirely your concern

 

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