Short-term Consumption of a Low-Fat Diet Beneficially Affects Plasma Lipid Concentrations Only When Accompanied by Weight Loss

Short-term Consumption of a Low-Fat Diet

Beneficially Affects Plasma Lipid Concentrations

Only When Accompanied by Weight Loss

Hypercholesterolemia, Low-Fat Diet, and Plasma Lipids

Alice H. Lichtenstein, Lynne M. Ausman, Wanda Carrasco, Jennifer L. Jenner,

Jose M. Ordovas, Ernst J. Schaefer

Abstract Study subjects (6 women and 5 men) over the age of 40 years with fasting low-density lipoprotein cholesterol concentrations >130 mg/dL were studied during three 5-week diet phases and one 10-week phase: baseline (36% fat: 13% saturated fatty acids [SFA], 12% monounsarurated fatty acids [MUFA], 8% polyunsaturated fatty acids [PUFA], and 128 mg cholesterol/1000 kcal); reduced fat (29% fat: 7% SFA 9% MUFA 11% PUFA and 85 mg cholesterol/1000 kcal); and two low fat (15% fat: 5% SFA 5% MUFA 3% PUFA and 73 mg cholesterol/1000 kcal). Body weight was maintained during the first three 5-week phases (baseline, reduced fat, and low fat [—• energy]) and decreased during the last 10-week phase when the low-fat diet was provided such that the subjects determined, in part, their caloric intake (low fat [I energy]). Mean body weight declined by 0.62±0.47 kg/wk during the first 5 weeks and 0.43±0.43 kg/wk during the second 5 weeks of the 10-week low-fat (I energy) period. Relative to the baseline diet, plasma cholesterol concentrations decreased from 226±33 to 195 + 19 (-13%), 208±22 (-7%), and 190±19 (-15%) mg/dL when the subjects consumed the reduced-fat, low-fat (-» energy), and low-fat (j energy) diets, respectively. Low-density lipoprotein cholesterol concentrations decreased

T

here is general agreement that the fat content of

the average diet should be reduced.

Reference

to such recommendations is not without

histor-ical basis.

Additionally, the general consensus appears

to be that cutting the saturated fat content of the diet

imparts the most benefit with respect to lowering

plasma cholesterol levels.35 The optimal level to which

the total and saturated fat content in the diet should be

reduced is far more controversial.610

Current National Cholesterol Education Program

(NCEP) dietary recommendations concerning fat are

relatively broad: total fat intake s30% and saturated fat

intake £10% of calories (step 1) or <.!% (step 2) of

calories, depending on initial plasma lipid levels and

initial response.1 Expected reductions in plasma lipid

concentrations include declines in both low-density

Received April 14, 1994; revision accepted August 5, 1994. From the Lipid Metabolism Laboratory, US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, Mass, and the School of Nutrition (L.M.A.), Tufts University, Medford, Mass.

Correspondence to Dr Alice H. Lichtenstein, USDA Human Nutrition Center on Aging at Tufts University, 711 Washington St, Boston, MA 02111.

O 1994 American Heart Association, Inc.

from 158±28 to 128±16 (-18%), 134±17 (-14%), and 119+15 (-23%) mg/dL when the subjects consumed the reduced-fat, low-fat (-» energy), and low-fat (| energy) diets, respectivery. High-density lipoprotein cholesterol concentra-tions decreased from 48±11 to 42±9 (-10%), 35±7 (-25%), and 38±8 (-18%) mg/dL when the subjects consumed the reduced-fat, low-fat (-» energy), and low-fat (i energy) diets, respectively. Triglyceride concentrations increased from 110+32 to 115±31 (8%), 188±76 (75%), and 130±32 (22%) mg/dL when the subjects consumed the reduced-fat, low-fat (-» energy), and low-fat (j energy) diets, respectively. Maxi-mal changes in plasma lipid concentrations were observed after the first 5 weeks of the low-fat (| energy) diet phase despite continued weight loss throughout the entire 10-week diet period. These data suggest that very-low-fat diets (15% of calories) beneficially affect plasma lipid profiles relative to the baseline (36% of calories) or reduced-fat (29% of calories) diets only when accompanied by weight loss. (Arterioscler Thromb. 1994;14:1751-1760.)

Key Words • cholesterol low fat • weight loss

triglyceride diet •

lipoprotein cholesterol (LDL-C) and high-density

lipo-protein cholesterol (HDL-C) levels.31115 The advocates

of a moderate approach to dietary management, ie,

maintaining the total fat content of the diet at or about

30% of calories, cite concern over the lowering of

HDL-C concentrations and theoretical increased risk of

cardiovascular disease.8-9 Other workers have suggested

that diet-induced decreases in HDL concentrations

should not be interpreted equivalentry to low HDL

concentrations independent of diet.

Although diets

relatively high in monounsaturated fatty acids (MUFA)

have been suggested as selectively lowering LDL-C

without altering HDL-C concentrations, confirmation

of this observation when the total fat content of the

diet is within the recommended guidelines has been

inconsistent.

When the fat content of the diet is reduced it can be

replaced by protein, complex carbohydrate, or nothing.

Evidence suggests that the protein intake of the United

States population as a whole meets the recommended

dietary allowances.

It is unlikely that increasing the

protein intake would have a direct beneficial effect. Due

to the frequent concurrence of fat in foods that are

relatively high in protein, any increase in protein intake

would make complying with a low-fat diet more difficult unless specially modified products were consumed. Therefore, most recommendations advocate replacing fat with complex carbohydrate.1-34 Potential benefits to

this approach include increased nutrient density and fiber content in the diet35-36 and possibly satiety or a

feeling of fullness depending on the source of supple-mental carbohydrate.37-38 Disadvantages include, at

least transiently, an increase in plasma triglyceride concentrations and a concomitant decrease in HDL-C concentrations.3-4-39-43 An increase in plasma

triglycer-ide concentration can be avotriglycer-ided by small incremental increases as opposed to one big increase in the carbo-hydrate content of the diet.44

The third alternative when reducing the fat content of the diet is to not replace it with anything. The approach of radically reducing the fat content of the diet without specific efforts to maintain body weight has been reported to result in a spontaneous decrease in caloric intake and weight loss745-46 and, when

as-sessed, a dramatic lowering of plasma lipid concentra-tions and reduction in the severity of coronary athero-sclerotic lesions.6'7'47'48

Taking the above points into consideration, a study was designed to investigate the effects of consuming a diet containing 36% of calories as fat with a fatty acid composition approximating that currently consumed in the United States, a reduced-fat diet containing 29% of calories as fat designed to met NCEP step 2 guidelines (reduced fat), and a low-fat diet containing 15% of calories as fat (low fat). The latter diet was consumed either at levels to maintain body weight (as were the baseline and reduced-fat diets) or at levels determined, in part, by the individual volunteer. The study volun-teers were middle-aged and older men and women with moderately elevated plasma lipid levels and mean body mass indexes. The results of the study suggest that drastically reducing the fat content of the diet had an unfavorable effect on plasma lipoprotein concentrations unless accompanied by weight loss. Additionally, maxi-mal effects of dietary modification on plasma lipopro-tein concentrations were realized only during the initial weight-loss period.

Methods Subjects

Eleven (6 female and 5 male) subjects with a mean age of 60 years (range, 44 to 78 years) with LDL-C concentrations greater than 130 mg/dL underwent a medical history, physical examination, and had clinical chemical analyses performed before enrollment in the study. The subjects had no evidence of any chronic illness, including hepatic, renal, thyroid, or cardiac dysfunction. They did not smoke, indicated they were able to abstain from alcohol for the duration of the study period, and were not taking medication known to affect plasma lipid levels (eg, lipid-lowering drugs, /3-adrenergic blocking agents, diuretics, or hormones). All the women were post-menopausal. These subjects were recruited as part of a larger study to investigate the effects of fatty acid and cholesterol intake on plasma lipid concentrations.14-49-51 The initial study

cohort was composed of 15 subjects, 4 of whom chose not to participate in the later additional phases of the study. Elimi-nating their screening data from the remaining subjects' data did not significantly change the overall characteristics of the study group. This protocol has been approved by the Human

Investigation Review Committee of the New England Medical Center and Tufts University.

Experimental Design

All subjects participated in each of three 5-week study phases. They first consumed a diet similar in fat content to that currently consumed in the United States (baseline), which provided 17% of calories as protein, 48% as carbohydrate, 36% as fat (13% saturated fatty acids [SFA], 12% MUFA, 8% polyunsaturated fatty acids [PUFA]), and 128 mg cholesterol/ 1000 kcal. The subjects next consumed a reduced-fat diet (reduced fat) containing 17% of calories as protein, 53% as carbohydrate, 29% as fat (7% SFA, 9% MUFA, 11% PUFA), and 85 mg cholesterol/1000 kcal. During the third 5-week period, the subjects ate a low-fat (-» energy) diet containing 17% protein, 68% carbohydrate, 15% fat (5% SFA, 5% MUFA, 3% PUFA), and 73 mg cholesterol/1000 kcal. Each diet was consumed for 5 weeks at caloric levels that main-tained stable body weights. Plasma lipid levels stabilize after 4 weeks on a diet,52 and there is no effect of order of diets on

study outcome.51 Mean caloric intake was 2679±608 kcal

(range, 2000 to 4000 kcal) during the first three phases. The fourth phase of the study (low fat [| energy]) was designed to provide the same nutrient composition as the low-fat (third) phase, but it allowed the subjects to determine, in part, their caloric intake. This final diet was conceived to test the hypothesis that drastically reducing the fat content of the diet will result in spontaneous weight loss and subse-quently beneficially affect plasma lipid profiles. To accomplish this aim within the context of a metabolic study protocol, subjects were provided with and required to consume two thirds of the caloric intake they received during the low-fat (-» energy) phase. All food components of the diet were reduced proportionally. Participants were also provided with an addi-tional two thirds of their caloric intake in the form of 200-kcal portions of frozen entrees normally present in their diet, the composition of which was similar to that of the low-fat diet. The subjects were instructed that they had to consume the first two thirds of the food provided and could determine how much additional food they were to consume thereafter. In the most extreme cases they could have either consumed one third fewer or one third more calories than on the low-fat (-• energy) phase. When a subject reported that a food item was consumed subsequent to the previous visit ( s 3 days), it was replaced so that the additional food was always available. The study period for the fourth (low-fat [| energy]) phase was thus continued for an additional 5 weeks (10 weeks total) so that potential effects of changes in body weight on plasma lipid concentration could be better monitored. Data are reported for the first 5-week time point for comparisons with the other dietary phases and for the second 5-week time point for comparisons within that phase.

Triplicate preparations of each complete meal cycle (3 days) for each diet phase were analyzed by Hazleton Laboratories America, Inc. The composition, fatty acid profile, and choles-terol content of the diets are shown in Table 1. In general, there was good agreement between the analytical and calcu-lated data except for cholesterol, which was overestimated in the food composition tables.

All food and drink were provided by the Metabolic Re-search Unit of the US Department of Agriculture (USDA) Human Nutrition Research Center on Aging at Tufts Univer-sity for consumption on site or packaged for takeout. The subjects were required to report to the research unit a minimum of three times per week, have blood pressure and weight measured at each visit, and consume at least one meal on site each time. They were encouraged to maintain their habitual level of physical activity throughout the study period. Four times during the final week of study phases one through three or during weeks 5 and 10 of the low-fat (| energy) phase fasting blood samples were obtained for lipid and

TABLE 1 . Composition of the Study Diets As Determined by Chemical Analysis

TABLE 2. Baseline Characteristics of the Study Subjects

Diet

Variable Baseline Reduced Fat Low Fat

Protein, % Carbohydrate, % Fat, % SFA,% 12:0 14:0 16:0 18:0 MUFA, % 16:1 18:1 PUFA,% 18:2 n6 18:3 n3 20:4 n6 Cholesterol, mg/1000 kcaJ 16.5±0.5 48.1 ±2.9 35.6+2.4 12.90±1.97 0.37±0.03 1.45±0.22 6.86±0.96 3.29±0.67 12.17±1.60 0.05±0.10 11.16±1.29 7.94±0.75 6.95±0.66 0.82±0.06 0.06±0.01 128±21 17.4 53.3 29.4 6.90 0.09 0.04 4.33: 1.60 8.98: 0.30 8.40 11.21 10.67 0.40 0.05: t0.9 t2.4 t1.5 t0.60 t0.01 t0.04 t0.30 t0.21 t0.64 fcO.08 t0.55 t0.52 t0.53 t0.06 t0.01 16.9 68.0: 15.1: 5.01: 0.12d 0.47: 2.77d 1.36d 4.86d 0.24: 4.46: 2.54: 2.20: 0.26; 0.04: ±0.6 :2.6 :0.93 :0.02 :0.09 :0.46 :0.31 :0.657 :0.02 :0.64 :0.50 :0.42 :0.06 :0.01 85±4 73±3

SFA indicates saturated fatty acids; MUFA, monounsaturated tatty acids; and PUFA, polyunsaturated fatty acids. See "Meth-ods" for definitions of diets. Values are mean±SD; n=3.

tein determinations. On one day during the final week of the first three phases or during weeks 5 and 10 of the low-fat (J, energy) phase subjects consumed their three meals plus one snack at standardized intervals, and blood was sampled at 0, 5, 8, 10, and 24 hours.

Biochemical Analysis

Fasting (12-hour) blood was collected in tubes containing 0.1% EDTA, and very-low-density lipoprotein (VLDL) was isolated from plasma by a single ultracentrifugational spin at density 1.006 g/mL (39 000 rpm for 18 hours at 4°C). Plasma and the 1.006-g/mL infranate were assayed for total choles-terol and/or triglyceride with an Abbott Diagnostics ABA-200 bichromatic analyzer using enzymatic reagents.33 HDL-C was

measured as described,54 and non-HDL-C (total cholesterol

minus HDL-C) was determined in nonfasting plasma after HDL-C precipitation. Lipid assays were standardized through the Lipid Standardization Program of the Centers for Disease Control and Prevention, Atlanta, Ga. Within-run and be-tween-run coefficients of variation of these assays were less than 5%.

Apolipoprotein (apo) B was assayed with a noncompetitive, enzyme-linked assay by using immunopurified polyclonal an-tibodies53 in plasma after VLDL had been removed. Plasma

apoA-I was assayed in the same manner by using apoA-I polyclonal antibodies.56 Coefficients of variation for both

as-says were less than 5% within runs and less than 10% between runs. Assays were standardized with LDL containing only apoB and purified apoA-I with the protein content determined by amino add analysis. Lipoprotein(a) [Lp(a)] was quantified by using an enzyme-linked assay with a monoclonal antibody that did not cross-react with plasminogen as the first antibody and a polyclonal antibody as the second antibody that was directed against the apo(a) portion of the Lp(a) particle (Terumo Medical Corp). Lp(a) concentrations are expressed as total Lp(a) mass in milligrams per deciliter.57

Variable Women (n=6) Men (n=5) Mean Age, y 66±12 54±12 60±13 Body weight, kg 69+18 82±14 75+17 Height, cm 159±3 175±10 166±10 Body mass index, kg/m2 27.2+6 0 26.8±2.4 27.0±4.5 Total cholesterol, mg/dl 243+32 244±11 243±23 VLDL cholesterol, mg/dL 27+7 29±12 28±9 LDL-C, mg/dL 167±28 173±15 169±22 HDL-C, mg/dL 50+9 42±12 46±10 Triglycerides, mg/dL 135±35 144±61 139±46 TC/HDL-C 5.03±1.13 6.16±1.79 5.55±1.51

VLDL indicates very-low-density lipoprotein; LDL-C, low-den-sity lipoprotein cholesterol; HDL-C, high-denlow-den-sity lipoprotein cho-lesterol; and TC, total cholesterol. Values are mean±SD.

Statistical Analysis

The data were analyzed by using SAS (STATISTICAL ANALYSIS

SYSTEM; SAS Institute Inc) both for the IBM-compatible personal computer using version 6.04 and as run on a VAX mainframe (Digital Equipment Corp), PROC GLM was used for ANOVA procedures for repeated measures followed by Tukey's t test performed at the ^=.05, .01, and .001 levels of comparison.

Results

The mean age of the study subjects was 60 ±13 years (Table 2); all subjects had somewhat elevated body mass indexes. At the time of screening they had a mean LDL-C concentration of 169±22 mg/dL. The women tended to have higher HDL-C and lower LDL-C con-centrations than the men.

The consumption of the reduced-fat diet (29% of calories as fat) resulted in 13%, 18%, and 10% de-creases in total cholesterol, LDL-C, and HDL-C con-centrations, respectively, relative to the baseline diet (36% of calories as fat) (Table 3 and Fig 1). Changes in LDL apoB concentrations mirrored those of LDL-C. In contrast, despite a decrease in HDL-C concentrations, there was little change in the concentration of apoA-I. These changes resulted in similar total cholesterol/ HDL-C ratios but significantly lower LDL apoB/apoA-I ratios. No significant effects of consuming the reduced-fat diet on the concentrations of triglyceride and Lp(a) relative to the baseline diet were observed.

When the fat content of the diet was decreased to 15% of calories and consumed at isocaloric levels (low fat [-> energy]), there was a less favorable effect on plasma lipid levels than when the fat content of the diet was reduced to only 29% of calories. Relative to the baseline diet, there were 7%, 14%, and 25% decreases in total cholesterol, LDL-C, and HDL-C concentrations during the low-fat (-» energy) period (Table 3 and Fig 1). These changes were accompanied by dramatic in-creases in VLDL cholesterol (95%) and triglyceride (75%) concentrations.

Relative to the baseline diet the decrease in LDL apoB concentrations (-17%) was similar to that ob-served for LDL-C concentrations (-14%); however, as

TABLE 3. Effects of Dietary Fat Reduction and Weight Loss on Plasma Upld and Upoproteln Concentrations Upld or Upoproteln Total cholesterol VLDL cholesterol LDL-C HDL-C Triglycerides TC/HDL LDLapoB ApoA-l Lp(a)§ LDL apoB/apoA-l Baseline 226±33* 21 ±6* 158±28* 48±11* 110±32t 4.99±1.30t 105±23* 131 ±23* 16±21* 0.82±0.21* Reduced Fat 195±19tt (-13+7) 25±3t* (33±48) 128 + 16+* (-18 ±9) 42±9t (-10±6) 115+311" (8 ±25) 4.78±0.97t 82±18t (-20 + 16) 129+20*t (-1+9) 17±23* (7±14) 0.65+0.19+ Diet Low Fat (—Energy) 208±22t (-7±10) 39±15* (95±69) 134±17t (-14±12) 35±7t (-25±10) 188±76* (75±51) 6.13±1.43* 85±13t (-17±13) 116±14t+ (-10+10) 15±21* (-2±25) 0.74±0.13*t Low Fat ( i Energy) 190±19+ (-15±8) 32±9*t (64 ±62) 119±15+ (-23±9) 38±8t* (-18±10) 130±32f (22 ±25) 5.13±1.09t 74±18t (-23±24) 111 =t 15t* (-12±10) 13±24t (-27±33) 0.68±0.19*t VLDL indicates very-low-density lipoproteln; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; TC, total cholesterol; apo, apolipoprotein; and Lp(a), lipopro-tein(a). Values are in milligrams per deciliter (mean percent difference from baseline). See "Methods" for definitions of diets.

Values without a common symbol were significantly different at P<.05 using Tukey's f test. §Raw data were transformed to k>g10 values before statistical analysis. Values are mean±SD.

we observed during consumption of the reduced-fat

diet, the decrease in apoA-I levels (—10%) was

atten-uated relative to the decrease in HDL-C concentrations

(-25%). The total cholesterol/HDL-C ratio was

signif-icantly higher during consumption of the low-fat (—>

energy) diet, whereas the LDL apoB/apoA-I ratio was

intermediate between the previous two phases. Similar

to during the reduced-fat diet phase, Lp(a)

concentra-tions were not significantly affected during the period

when the subjects consumed the low-fat (-» energy)

diet.

As intended by the study design, there was little

change in body weight during the reduced-fat and low-fat

(-• energy) periods (-0.06±0.27 and -0.14±0.20 kg/wk,

respectively). Allowing the subjects to adjust their caloric

intake during the low-fat ( | energy) diet resulted in a

significant weight loss. On average, the subjects reduced

their caloric intake to a level that resulted in an average

weight loss of 0.62 ±0.47 kg/wk during the first 5-week

phase of the low-fat (I energy) diet period. This result

confirmed the anecdotal comments made by the study

subjects that suggested that the amount of food provided

during the low-fat (—» energy) diet phase that was

necessary to maintain body weight was more than they

were comfortable consuming and that subjective feelings

of hunger were satisfied with a lower caloric intake. The

effects of consuming the low-fat (j energy) diet and

weight loss on plasma lipid concentrations were striking.

At the end of the first 5 weeks of the low-fat ( |

ener-gy) diet there was a 15% decrease in total cholesterol, a

23% decrease in LDL-C, and an 18% decrease in

HDL-C concentrations relative to baseline (Table 3 and

Fig 1). These decreases in cholesterol concentrations,

with the exception of HDL-C, were significantly greater

than those observed for any of the other diet phases.

Plasma triglyceride concentrations at the end of the first

5 weeks of the low-fat (j energy) diet were not

signifi-cantly different from levels observed at the end of the

baseline and reduced-fat periods. VLDL cholesterol

concentrations remained somewhat elevated above

baseline levels.

During the first 5 weeks of the low-fat ( | energy) diet

LDL apoB concentrations were reduced to a similar

extent as that observed for LDL-C concentrations.

Declines in apoA-I concentrations (-12%) were again

less dramatic than that observed for HDL-C

concentra-tions (-18%). The ratio of total cholesterol/HDL-C

was similar to the same ratio at the end of the baseline

period. In contrast, the ratio of LDL apoB/apoA-I

during the first 5 weeks of the low-fat (J, energy) diet

was somewhat lower than that observed during the

baseline period and similar to that observed during the

low-fat (-» energy) period.

Plasma lipid concentrations were monitored in the

postprandial state, when subjects consumed their three

meals plus one snack at standardized intervals (Table 4

o IT o o 160 75 o IT O 125 X o O 100 o O o BASE-U N E RfOUCED FAT LOW FAT - ENERGY LOW FAT I ENERGY BASE-LINE REDUCED FAT LOW FAT - ENERGY LOW FAT 1 ENERGY FIQ 1. Une plots of Individual plasma lipid concentrations at the end of each diet phase. See "Methods" for definitions of diets. LDL indicates low-density lipoprotein; HDL, high-density lipoprotein.

and Fig 2). Postprandial plasma cholesterol and

non-HDL-C concentrations were not significantly different

from fasting values. In contrast, HDL-C concentrations

consistently exhibited a postprandial fall of 5% to 7%,

which was significantly different from fasting levels over

all the diet phases.

Mean postprandial plasma triglyceride

concentra-tions (at 5-, 8-, and 10-hour time points) were

approx-imately twofold higher than fasting values and were

statistically different from fasting values for all diet

phases. By 24 hours plasma triglyceride concentrations

were statistically indistinguishable from the initial

fast-ing values regardless of dietary treatment.

The differences observed among diets with respect to

postprandial total cholesterol, non-HDL-C, HDL-C,

and triglyceride concentrations were similar to those

observed in the fasting state. Postprandial total

choles-terol concentrations were from lowest to highest when

the subjects consumed the low-fat (j, energy),

reduced-fat, low-fat (-» energy), and baseline diets. In general,

non-HDL-C concentrations were lowest when the

sub-jects consumed the low-fat ( | energy) and reduced-fat

diets and highest when they consumed the low-fat

(-> energy) and baseline diets. HDL-C concentrations

were from lowest to highest when the subjects

con-sumed the low-fat (—» energy), low-fat (j energy),

re-duced fat, and baseline diets. Postprandial triglyceride

concentrations were significantly higher at the end of

the low-fat (-» energy) diet than at the end of any of the

other diet periods.

The study subjects continued to consume the low-fat

( | energy) diet for an additional 5 weeks (Table 5).

Although there was a persistent loss of body weight,

albeit at a somewhat slower rate (0.62±0.47 versus

0.43±0.43 per week, first and second diet periods,

respectively), the greatest effect of weight loss on

plasma lipid and apolipoprotein concentrations

oc-curred after the first 5 weeks of the fourth study period.

Plasma lipid and apolipoprotein concentrations

re-mained remarkably stable during the second 5-week

period of the low-fat (J. energy) phase.

Discussion

Impressive observations have been made with respect

to the benefits of extremely low-fat diets on plasma lipid

concentrations and regression of atherosclerotic

plaque.6'7'58 Populations that normally consume low-fat

diets are generally reported to have lower plasma lipid

concentrations and rates of coronary heart disease than

those consuming higher fat diets.

In such populations

caloric intake tends to be lower and fiber intake higher

than in societies consuming higher fat diets, and obesity

is generally not cited as a major public health

prob-lem.

In general, the consumption of ad libitum

quantities of low-fat diets relative to higher fat diets

on an experimental basis is accompanied by weight

loss.45'46-6268 Increasing the fat intake of people who

habitually consume a low-fat diet has been reported to

result in weight gain and adverse effects on plasma

lipid concentrations.

The results of a recent

meta-anarysis of studies assessing the relation between

weight change and plasma lipid levels concluded that

weight loss is associated with an improvement of

plasma lipid profiles.

Taking these observations into consideration, we

investigated the effects of reduced-fat and low-fat

diets with and without weight loss on plasma lipid,

lipoprotein, and apolipoprotein concentrations.

Mid-dle-aged and elderly female and male subjects with

plasma LDL-C concentrations that indicated the need

for dietary modification were targeted, since this is the

group for which recommendations to reduce dietary

fat content are frequently made. (Although body mass

index was not a screening criterion, the group of

subjects participating in the study, qualifying on the

basis of having LDL-C levels above 130 mg/dL, had a

somewhat elevated mean body mass index [27.0±4.5]).

We do not have anthropometric measures of the study

subjects, and differences in body fat distribution could

have modified the effect of weight loss on their plasma

lipid levels. Given that limitation, the results of the

investigation suggest, relative to a baseline diet, that

when body weight was maintained, reducing the total

and saturated fat content of the diet in accordance

with the current NCEP step 2 guidelines resulted in a

significant decrease in total cholesterol, LDL-C, and

HDL-C concentrations. Further reducing the total fat

content of the diet under the same conditions also

resulted in decreased concentrations of total

choles-terol, LDL-C, and HDL-C, although the reductions in

total cholesterol and LDL-C were less dramatic and

the decrease in HDL-C greater than when the subjects

consumed the reduced-fat diet. Accompanying these

changes was a striking increase in plasma triglycerides

and VLDL cholesterol concentrations. The end result

was a less favorable plasma lipid profile with respect to

cardiovascular risk. Allowing the subjects to decrease

their caloric intake while maintaining the

TABLE 4. Postprandial Plasma Upld Response to Three Meals and On* Snack at the End of Each Diet Phase

Hours Postprandial 0 5 8 10 24 0 5 8 10 24 0 5 8 10 24 0 5 8 10 24 Baseline 226±32* 224 ±32* 223±34* 225 ±35* 227±35* 179±32* 179±33* 178±36* 180±37* 179±34* 48±11* 45±10* 45+10* 45+9* 48+11* 1O9±31t 174+92t 187±77*t 201 ±82*t 113±39t Reduced Fat Diet Low Fat ( ^ Energy) Total cholesterol 195±19t* 193±17f* 192±17t* 197±22f* 195±21f* 2O8±22t 209±23*t 208±22*t 207±26*t 210±24*t Non-HDL-C 153±16t 153±16t 153±17t 158±21f* 153±18t 43±9t 40±9t 39±8t 39±9t 41±8t 172 ±24* 175 ±24* 175 ±25* 173±28*t 174+24* HDL-C 35±7* 34 + 7* 33+7* 33+7* 36+7* Triglycerides 114±30t 180±71t 230±90* 239±142*t 121±38t 185+77* 248+113* 243±125* 259+109* 198+83* Low Fat (I Energy) 190±19* 185+20* 182±25* 182±23* 187±23** 152±19t 148±20t 145±23t 144±22t 148±22t 38±8* 37±6t* 37±8t* 37±7f* 39±7t* 129±33t 162±61t 141±51t 152±51t 126±34t HDL-C indicates htgh-density llpoproteln cholesterol; non-HDL-C, total cholesterol minus HDL-C. Values are mean±SD and are expressed in milligrams per deciliter; n=11. See "Methods" for definitions of diets.

ANOVA for each time point using data from all four diet groups showed a significant effect of diet (P<.05) for each variable at each time point. At each sampling time, mean values without a common symbol are significantly different using Tukey's f test at P<05.

A three-way ANOVA with main effects of diet, time, and subject showed that time was a significant variable for HDL-C and triglycerides only. Tukey's f test showed the results below. Values without a common symbol are significantly different at P<.01 for HDL-C and P<.001 for triglycerides.

Hours Postprandial HDL-C Triglycerides 10* 10* Of 24t 24t Ot

ent composition of the diet resulted in significantly

lower concentrations of total cholesterol and LDL-C,

a normalization of triglyceride concentration, and a

higher HDL-C concentration.

Of potential concern was the consistent decrease in

HDL-C concentrations, presumably resulting from the

decrease in saturated fat intake. This observation is not

without precedent.3'1115 In the current study this trend

was most pronounced during the period when the

subjects consumed the low-fat (-» energy) diet, but it

was observed at the end of the other dietary phases as

well. Significantly, in all cases apoA-I levels did not

decline at the same rate as HDL-C levels. This

obser-vation suggests that the number of HDL particles in the

circulation was maintained.

In contrast to changes in HDL-C and apo A-I levels,

LDL-C and LDL apoB concentrations tended to

change in a parallel manner regardless of the dietary

perturbation. These data suggest that the number of

particles but not the size of the particles was affected by

dietary modification of the magnitude induced in the

current studies. Additionally, when either the

-1 250 O 225 CE UJ

d

°

5

fat or low-fat (| energy) diets were consumed, the

relative change in LDL and LDL apoB concentrations

exceeded that of HDL-C or apoA-I.

When the subjects consumed the reduced-fat diet,

which was consistent with NCEP step 2 guidelines, total

cholesterol, LDL-C, and HDL-C concentrations

de-creased relative to the baseline diet. Further reducing

the fat content of the diet from 29% to 15% of calories

was achieved by eliminating most sources of added fat.

In keeping with the design of the study the actual foods

making up the diet were not altered. This resulted in a

large decrease in poryunsaturated fat, a moderate

de-crease in monounsaturated fat, and a smaller dede-crease

in saturated fat in the diet. These changes themselves

may have accounted for the greater decrease in HDL-C

than LDL-C when subjects consumed the low-fat (—>

energy) diet. However, at extremely low levels of total

fat in the diet, observations pertaining to the differential

effects of the different individuals or classes of fatty

acids may not be valid.

Decreasing the fat content of the diet and increasing

the carbohydrate content likely resulted in a

concomi-tant increase in the level of fiber in the diet,35-36 a

variable that was not specifically addressed in the

cur-rent study. Independent effects of total and soluble fiber

on plasma lipid levels have been documented.7173

How-ever, the primary aim of the present investigation was to

assess the effects of varying the fat content of the diet

with commonly available foods. An alternate approach,

to isolate the independent effects of fat and fiber, would

have necessitated artificially keeping the fiber constant

while altering the fat content of the diet, which would

have answered a different but interesting experimental

question.

The trigfyceride levels remained relatively stable

when the carbohydrate content of the diet was increased

FIG 2. Line plots of mean postprandial total cholesterol, non-high-density llpoprotein (HDL) cholesterol, HDL cho-lesterol, and triglyceride values after subjects were ted a baseline (circle), reduced-fat (triangle), low-fat (-> energy) (square), or low-fat (J. energy) (diamond) diet. See "Meth-ods" for definitions of diets. *P<.05 at 5, 8, and 10 hours postprandial vs 0 and 24 hours.

20 24

by 5% of calories to compensate for the decrease in the

fat content of the diet. When the carbohydrate content

of the diet was further increased by 15% there was a

dramatic increase in plasma triglyceride levels, perhaps

secondary to an increase in insulin levels induced by the

increased carbohydrate content. We cannot answer the

question of whether these levels would have decreased

had the subjects consumed the diet for longer periods of

time. Additionally, we cannot address the issue of what

effect increasing the fiber content of the diet may have

on plasma lipid levels. But we did observe that when the

subjects consumed the low-fat (j. energy) diet the

increase in plasma triglyceride levels was attenuated to

the point of not being significantly different from either

the baseline or reduced-fat diet phases. This

observa-tion was most striking when the postprandial plasma

triglyceride levels were examined. In general, maximal

concentrations of plasma triglycerides were observed in

all diet phases at the 8- and 10-hour time points of the

study and were lowest when the subjects consumed the

low-fat (| energy) diet. These data suggest that the

dramatic increase in plasma triglyceride concentrations

observed after consumption of the low-fat (-» energy)

diet when assessed in the fasting state is far less than

when monitored in the postprandial state.

The baseline, reduced-fat, and low-fat (-» energy)

phases each lasted for 5 weeks. This time period is

adequate to achieve stable plasma lipid levels when

body weight remains constant.52 During the 10-week

low-fat (i energy) phase, plasma lipid concentrations

appeared to reach stable levels by the fifth week.

However, this apparent plateau in the lipid levels was

maintained despite the continued trend of the study

subjects to decrease their body weight throughout the

entire period. Whether continuing the study would have

resulted in continued alterations in plasma lipid

TABLE 5. Effects of Continued Weight Loss on Plasma Upld and Upoproteln Concentrations

Upld or Upoproteln Total cholesterol VLDL cholesterol LDL-C HDL-C

Trig lyce rides

TC/HDL LDLapoB ApoA-l Lp(a)* LDL apoB/apoA-l Low Fat (1 Energy), Weeks 1-5 190+19 (-15±8%) 32±9 (64 ±62%) 119±15 (-23+9%) 38±8 (-18±10%) 130±32 (22 ±25%) 5.13±1.09 74±18 (-23+24%) 111±15 13+24 (-27±33%) 0.68±0.19 Diet Low Fat (I Energy), Weeks 6-10 190±17 (-15±9%) 31 ±7 (66±87%) 121 ±15 (-23 + 10%) 38±7 (-18±9%) 120±32 (15±39%) 5.09±1.00 86±17 (-7±20%) 110±10 12±21 (-37±26%) 0.80±0.20 VLDL Indicates very-low-density lipoproteln; LDL-C, low-den-sity lipoproteln cholesterol; HDL-C, high-denlow-den-sity lipoprotein cho-lesterol; TC, total chocho-lesterol; apo, apollpoproteln; and Lp(a), lipoprotein(a). Values are mean±SD and are expressed in milligrams per deciliter (mean percent difference from baseline). See "Methods" for definitions of diets.

*Raw data were transformed to logt 0 values before statistical analysis.

centrations clearly needs to be investigated. In addition, at what level plasma lipids stabilize once lower body weights are achieved and maintained remains to be determined.

Consuming a low-fat diet in the absence of specific efforts to maintain a constant body weight resulted in weight loss. No apparent relation between the magni-tude of body weight change and change in plasma lipid concentrations was identified. A larger sample size would have been necessary to more thoroughly assess such issues.

The present study was designed to study the effect of moderate and radical reductions in fat intake on plasma measures of cardiovascular risk. The data suggest, at least in the short term, that diets consistent with NCEP step 2 guidelines result in significant reductions in plasma lipid concentrations; however, radical reductions in fat intake have a beneficial effect on plasma lipid profiles only when accompanied by weight loss.

Acknowledgments

This work was supported by contract 53-3K06-5-10 from the USDA, grant HL 39326 from the National Institutes of Health, Bethesda, Md, and by a grant from the American Heart

Disease Prevention Foundation, Inc, Fairfax, Va. The contents of this publication do not necessarily reflect the views or policies of the USDA nor does mention of trade names, commercial products, or organizations imply endorsement by the US government. The authors would like to thank the staff of the Metabolic Research Unit for the expert care provided to the study subjects and gratefully acknowledge the cooperation of the study subjects, without whom this investigation would not have been possible.

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