SOURCE: http://www.ajcn.org/cgi/content/full/80/5/1102

Saturated fat prevents coronary artery disease? An American paradox

Robert H Knopp and Barbara M Retzlaff

It is an article of faith that saturated fat raises LDL cholesterol
and accelerates coronary artery disease, whereas unsaturated fatty
acids have the opposite effect (1, 2). One of the earliest and most
convincing studies of the better efficacy of unsaturated than of
saturated fat in reducing cholesterol and heart disease is the Finnish
Mental Hospital Study conducted in the 12 y between 1959 and 1971. In
this study, the usual high-saturated-fat institutional diet was
compared with an equally high-fat diet in which the saturated fat in
dairy products was replaced with soybean oil and soft margarine and
polyunsaturated fats were used in cooking. Each diet was provided for
6 y and then the alternate diet was provided for the next 6 y (3).
After a comparison of the effects of the 2 diets in both men and
women, the incidence of coronary artery disease was lower by 50% and
65% after the consumption of polyunsaturated fat in the 2 hospitals.

In this issue of the Journal, Mozaffarian et al (4) report the
opposite association. They found that a higher saturated fat intake is
associated with less progression of coronary artery disease according
to quantitative angiography. How can this paradox be explained? In
food-frequency questionnaires, saturated fat intake is more precisely
estimated than is total fat. If saturated fat is more precisely
estimated, it will associate more strongly in statistical analyses
with the outcome variable, even though other variables--such as total
fat or carbohydrate--could be more relevant physiologically. We believe
that these possibilities deserve a closer look.

Unlike the diet used in the Finnish Mental Hospital Study, the diet
described by Mozaffarian et al was low in fat, averaging 25% of
energy. The study subjects were women with coronary artery disease:
most were hypertensive, many had diabetes (19-31%), their body mass
index (kg/m2) ranged from 29 to 30, and their lipid profile indicated
combined hyperlipidemia (triacylglycerol concentration: 200 mg/dL; HDL-
cholesterol concentration: 40-50 mg/dL; above-average LDL
concentration: 135-141 mg/dL); these characteristics are consistent
with the metabolic syndrome. In addition, two-thirds of these women
were taking sex hormones. The importance of each of these points is
addressed below.

What are the effects of a low-fat, high-carbohydrate diet in
comparison with those of a higher-fat, lower-carbohydrate diet? The
response differs by the 2 main types of hyperlipidemia: simple
hypercholesterolemia and combined hyperlipidemia. In our studies of
simple hypercholesterolemia in men, a fat intake <25% of energy and a
carbohydrate intake >60% of energy was associated with a sustained
increase in triacylglycerol of 40%, a decrease in HDL cholesterol of
3.5%, and no further decrease in LDL in comparison with higher fat
intakes (5). In contrast, a low-fat diet in persons with combined
hyperlipidemia caused no worsening of triacylglycerol or HDL, but
intakes of fat >40% of energy and of carbohydrate <45% of energy for 2
y were associated with a lower triacylglycerol concentration at a
stable weight (6). In the subjects of Mozaffarian et al, a greater
saturated fat intake paralleled a total fat intake, which ranged from
18% to 32% of energy in the first to fourth quartiles. Modest
favorable trends in triacylglycerol and HDL-cholesterol concentrations
were observed with higher fat intakes.

Triacylglycerol and HDL-cholesterol concentrations are stronger
predictors of coronary artery disease in women, whereas the LDL-
cholesterol concentration is a stronger predictor in men (7). Because
VLDL triacylglycerol secretion and removal rates in healthy women are
double those of men (8), conditions impairing lipoprotein removal
would be expected to exaggerate the hyperlipidemic response in women
as compared with that in men (9). This sex difference is seen with the
development of diabetes. The increment in lipids is greater in women
than in men and is associated with a greater increment in coronary
artery disease risk in women than in men (9). Similarly, the
development of insulin resistance and obesity is associated with a
greater lipoprotein increment in women than in men (10). The
exaggerated decreases in HDL- and HDL2-cholesterol concentrations
observed with the consumption of a low-fat Step II diet in women but
not in men appear to be another facet of this effect (11).

The failure of female sex hormones to prevent coronary artery disease
has been a great disappointment (9). This effect might also be due to
an estrogen-induced increase in lipoprotein entry against a fixed or
impaired rate of lipoprotein removal, as might be expected in women
with the metabolic syndrome and coronary artery disease.

Would saturated fat still be bad for anyone? Not necessarily. The
effect of saturated fat and cholesterol ingestion in the form of 4
eggs/d for 1 mo in obese, insulin-resistant subjects is 33% of that
seen in lean, insulin-sensitive subjects, likely because of diminished
cholesterol absorption (12). Thus, the classic effects of saturated
fat as compared with those of unsaturated fat seen in the Finnish
Mental Hospital Study are likely blunted in the subjects of
Mozaffarian et al, whereas the effects of low fat and high
carbohydrate intakes on triacylglycerol and HDL-cholesterol
concentrations appear to be exaggerated by the interactions of female
sex, exogenous sex hormones, and the metabolic syndrome. A major
effect on cardiovascular disease risk would be the result of
hypertriglyceridemia and low HDL-cholesterol concentrations, which are
attenuated by an increase in saturated fat intake itself or in total
fat intake, for which saturated fat is a more statistically stable
surrogate (4).

In conclusion, the hypothesis-generating report of Mozaffarian et al
draws attention to the different effects of diet on lipoprotein
physiology and cardiovascular disease risk. These effects include the
paradox that a high-fat, high-saturated fat diet is associated with
diminished coronary artery disease progression in women with the
metabolic syndrome, a condition that is epidemic in the United States.
This paradox presents a challenge to differentiate the effects of
dietary fat on lipoproteins and cardiovascular disease risk in men and
women, in the different lipid disorders, and in the metabolic
syndrome.