x-no-archive: yes
More on fat and CVD:
J Nutr. 2002 Jul; 132(7): 1879-85. Related Articles, Links
A ketogenic diet favorably affects serum biomarkers for cardiovascular
disease in normal-weight men.
Sharman MJ, Kraemer WJ, Love DM, Avery NG, Gomez AL, Scheett TP, Volek JS.
Human Performance Laboratory, Department of Kinesiology, University of
Connecticut, Storrs 06269-1110, USA.
Very low-carbohydrate (ketogenic) diets are popular yet little is known
regarding the effects on serum biomarkers for cardiovascular disease
(CVD). This study examined the effects of a 6-wk ketogenic diet on
fasting and postprandial serum biomarkers in 20 normal-weight,
normolipidemic men. Twelve men switched from their habitual diet (17%
protein, 47% carbohydrate and 32% fat) to a ketogenic diet (30% protein,
8% carbohydrate and 61% fat) and eight control subjects consumed their
habitual diet for 6 wk. Fasting blood lipids,
insulin, LDL particle
size, oxidized LDL and postprandial triacylglycerol (TAG) and insulin
responses to a fat-rich meal were determined before and after treatment.
There were significant decreases in fasting serum TAG (-33%),
postprandial lipemia after a fat-rich meal (-29%), and fasting serum
insulin concentrations (-34%) after men consumed the ketogenic diet.
Fasting serum total and LDL cholesterol and oxidized LDL were unaffected
and HDL cholesterol tended to increase with the ketogenic diet (+11.5%;
P = 0.066). In subjects with a predominance of small LDL particles
pattern B, there were significant increases in mean and peak LDL
particle diameter and the percentage of LDL-1 after the ketogenic diet.
There were no significant changes in blood lipids in the control group.
To our knowledge this is the first study to document the effects of a
ketogenic diet on fasting and postprandial CVD biomarkers independent of
weight loss. The results suggest that a short-term ketogenic diet does
not have a deleterious effect on CVD risk profile and may improve the
lipid disorders characteristic of atherogenic dyslipidemia.
PMID: 12097663 [PubMed - indexed for MEDLINE]
Saturated fat prevents coronary artery disease? An American paradox1,2
Robert H Knopp and Barbara M Retzlaff
1 From the Northwest Lipid Research Clinic, University of Washington
School of Medicine, Seattle
2 Address reprint requests to RH Knopp, Northwest Lipid Research
Clinic, University of Washington, School of Medicine, 325 9th Avenue,
Seattle, WA 98104. E-mail:
rhknopp@u.washington.edu.
See corresponding article on page 1175.
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.
REFERENCES
Kinsell LW, Michaels GD, Cochrane GC, Partridge JW, Jahn JP, Balch HE.
Effect of vegetable fat on hypercholesterolemia and
hyperphospholipidemia: observations on diabetic and nondiabetic
subjects given diets high in vegetable fat and protein. Diabetes
1954;3:113-9.[Medline]
Grundy SM, Denke MA. Dietary influences on serum lipids and
lipoproteins. J Lipid Res 1990;31:1149-72.[Abstract]
Miettinen M, Turpeinen O, Karvonen MJ, Elosuo R, Paavilainen E. Effect
of cholesterol-lowering diet on mortality from coronary heart-disease
and other causes. A twelve-year clinical trial in men and women. Lancet
1972;2:835-8.[Medline]
Mozaffarian D, Rimm EB, Herrington DM. Dietary fats, carbohydrate, and
progression of coronary atherosclerosis in postmenopausal women. Am J
Clin Nutr 2004;80:1175-84.[Abstract/Free Full Text]
Knopp RH, Walden CE, Retzlaff BM, et al. Long-term cholesterol-lowering
effects of 4 fat-restricted diets in hypercholesterolemic and combined
hyperlipidemic men. The Dietary Alternatives Study. JAMA
1997;278:1509-15.[Abstract]
Retzlaff BM, Walden CE, Dowdy AA, McCann BS, Anderson KV, Knopp RH.
Changes in plasma triacylglycerol concentrations among free-living
hyperlipidemic men adopting different carbohydrate intakes over 2 y:
the Dietary Alternatives Study. Am J Clin Nutr
1995;62:988-95.[Abstract]
Knopp RH, Zhu X, Bonet B. Effects of estrogens on lipoprotein
metabolism and cardiovascular disease in women. Atherosclerosis
1994;110(suppl):S83-91.[Medline]
Mittendorfer B, Patterson BW, Klein S. Effect of sex and obesity on
basal VLDL-triacylglycerol kinetics. Am J Clin Nutr
2003;77:573-9.[Abstract/Free Full Text]
Barrett-Connor E, Giardina EG, Gitt AK, Gudat U, Steinberg HO, Tschoepe
D. Women and heart disease: the role of diabetes and hyperglycemia.
Arch Intern Med 2004;164:934-42.[Abstract/Free Full Text]
Aikawa K, Retzlaff B, Fish B, et al. Dyslipidemia of insulin resistance
and obesity: gender differences. Circulation 2002;106(suppl 2):II-75
(abstr 377).
Walden CE, Retzlaff BM, Buck BL, Wallick S, McCann BS, Knopp RH.
Differential effect of the National Cholesterol Education Program
(NCEP) Step II diet on HDL cholesterol, its subfractions, and
apoprotein A-I levels in hypercholesterolemic women and men after 1
year: the beFIT Study. Arterioscler Thromb Vasc Biol
2000;20:1580-7.[Abstract/Free Full Text]
Knopp RH, Retzlaff B, Fish B, et al. Effects of insulin resistance and
obesity on lipoproteins and sensitivity to egg feeding. Arterioscler
Thromb Vasc Biol 2003;23:1437-43.[Abstract/Free Full Text]
---
Diabetes, Cholesterol & Heart Disease 