|
|
||||||||
Original Research Communications |
1 From Strategic Research and Development, Ross Products Division, Abbott Laboratories, Columbus, OH; the Department of Nutrition, Georgia State University, Atlanta; the Nutrition Department, The Pennsylvania State University, University Park; Aeterna Laboratories, Quebec City, Canada; and the Department of Community and Preventive Medicine, University of Rochester Medical Center, Rochester, NY.
2 Supported in part by Ross Products Division, Abbott Laboratories, Columbus, OH, and NIH grant DK50156 (to BJR).
3 Address reprint requests to VA Mustad, Ross Products Division, Abbott Laboratories Medical Nutrition R&D, 625 Cleveland Avenue, Department 105670, RP3-2 Columbus, OH 43215. E-mail: Vikkie.Mustad{at}rossnutrition.com.
| ABSTRACT |
|---|
|
|
|---|
Objective: Our objective was to compare lipid and lipoprotein responses to changes in total fat, saturated fatty acids (SFAs), and cholesterol in subjects consuming an SFD or LFD.
Design: Twenty-one healthy subjects consumed controlled diets representative of an average American diet [AAD; 37% of energy from fat (15% from SFAs), and <50 mg cholesterol/MJ] or a National Cholesterol Education Program (NCEP) Step II diet [26% fat (5% from SFAs) and <25 mg cholesterol/MJ]. Other nutrients were similar between diets. Diets were consumed for 23 d in a randomized, crossover design.
Results: For the AAD and NCEP Step II diet, there were no significant differences in lipids and apolipoproteins when the LFD or SFD versions were consumed. In contrast, consumption of the SFD was associated with significantly lower total cholesterol and triacylglycerols than was consumption of the corresponding AAD or Step II LFD (P < 0.05). Subjective ratings of satiety, hunger, and quality of life between diet forms did not differ significantly.
Conclusions: Both LFDs and SFDs yield quantitatively similar cholesterolemic responses to changes in dietary fat, SFAs, and cholesterol. LFDs may offer advantages because they provide easily administered, complete, balanced nutrition without affecting satiety.
Key Words: Liquid-formula diets fat saturated fat blood cholesterol satiety human food intake solid food lipids
| INTRODUCTION |
|---|
|
|
|---|
An attractive alternative is the use of nutritionally complete liquid-formula diets (LFDs). These diets are well suited for use in controlled feeding studies because they provide accurate and constant intakes of energy, macronutrients, vitamins, and minerals. LFDs are convenient, easy to deliver, and homogeneous, facilitating precise delivery of fatty acids and other nutrients of interest.
Many of the classic studies that evaluated the effects of dietary fatty acids and cholesterol effects on serum cholesterol concentrations used LFDs. The landmark work of Ahrens et al (3, 4) and Beveridge et al (5, 6) evaluated serum lipid effects by using LFDs containing various amounts and types of fat. Connor et al (7) also used LFDs to investigate steroid and bile acid excretion in men fed an LFD containing different oils. More recently, Grundy's group (811) used LFDs extensively in studies designed to examine cholesterolemic effects of individual fatty acids. Such experiments using LFDs, however, have not been without criticism (12). Hegsted and Nicolosi (13) described "unusual findings," such as a drop in serum cholesterol, that have been observed in some studies even when a major part of the total fat in the formula was saturated. The unexpected effects of LFDs in some studies may have been due, in part, to the low concentration or absence of cholesterol in the formula; different amounts of complex carbohydrates, dietary fiber, or other micronutrients; or differences in digestion and metabolism of liquid compared with solid foods.
Although there is considerable precedent for the use of LFDs in studying the effects of dietary fats and fatty acids on serum cholesterol concentrations, there has been no direct comparison of the cholesterolemic response to solid-food diets (SFDs) and LFDs. Thus, the present study was conducted to directly compare the blood lipid and lipoprotein responses to changes in total fat, saturated fatty acids (SFAs), and cholesterol in healthy subjects consuming SFDs or LFDs. The influence of the form of the diet (solid or liquid) and composition (varying amounts of total fat) on subjective ratings of hunger and satiety were also assessed.
| SUBJECTS AND METHODS |
|---|
|
|
|---|
25th and 50th percentiles from the third National Health and Nutrition Examination Survey reference population; 14), if their HDL-cholesterol concentration fell between the 10th and 90th percentiles, and if their triacylglycerol concentration was below the 90th percentile (percentiles adjusted for sex, age, and race) (15). Subjects were considered healthy on the basis of blood chemistry analysis and a self-administered health-screening questionnaire. All potential subjects sampled the LFD during the screening phase. Those who passed the initial screening and otherwise qualified for the study participated in a 3-d run-in period, during which they consumed the LFD for 100% of their total energy needs. This run-in period was intended to help potential subjects determine whether they liked the LFD and would be able to comply with this diet condition. After the trial period, subjects confirmed their willingness to participate in the study. The study protocol was approved by the Institutional Review Board of The Pennsylvania State University and informed, written consent was obtained from each subject.
Design
Subjects were recruited in groups of 4 to maintain balance in this 4 x 4 period randomized crossover study. Each of the 4 test diets was consumed for 23 d with a 7-d washout period between experimental diet periods. Breakfast and dinner were consumed under the supervision of the study's staff at the Nutrition Department's Metabolic Diet Study Center. Subjects reported to the dining facility at preset times (ie, between 0630 and 0930 for breakfast and between 1630 and 1830 for dinner). Lunch and snacks were packed for each individual subject, which they consumed where convenient except on days when satiety assessments were made (see below). Overall, subjects consumed >75% of their daily intake under staff supervision. Subjects were allowed to consume unlimited quantities of non-energy-containing beverages (ie, water and diet drinks) throughout the day. During the study, body weight was monitored daily and energy intake adjusted so that each subject maintained a constant weight. Subjects were instructed to maintain their normal physical activity levels throughout the study. A trained phlebotomist drew fasting blood samples (20 mL) by venipuncture on days 22 and 24 of each experimental diet phase for lipid and lipoprotein analyses. Serum was isolated from whole blood by centrifugation at 3000 x g and 4°C for 20 min and aliquots were stored in cryovials at 80°C until analyzed.
Diets
The 2 study diets were designed to mimic an average American diet [AAD; 37% of energy from fat (15% from SFAs) and <50 mg cholesterol/MJ] and a National Cholesterol Education Program (NCEP) Step II diet [26% of energy from fat (5% from SFAs) and <25 mg cholesterol/MJ]. Both diets were provided either as whole-food diets (ie, SFDs) made up of commonly available foods or as defined LFDs (Ross Products Division, Abbott Laboratories, Columbus, OH). The LFDs were formulated to match the nutrient composition of the whole-food diets and were based on the estimated average nutrient content of 7 sample menus created by using the NDS programs (version 2.8/10/25; Nutrition Coordinating Center, University of Minnesota, Minneapolis).
The nutrient composition of the diets was matched as closely as possible with respect to the estimated macro- and micronutrient contents, including total fat and fatty acid composition, cholesterol (mg/MJ), protein source (90% animal, 10% plant), and fiber distribution (33% soluble, 66% insoluble). Vitamin and mineral contents of all diets met recommended intakes. The nutrient composition of the 2 experimental LFDs was evaluated by using Association of Official Analytical Chemists (AOAC) methods for protein, carbohydrate, total fat, fatty acids, cholesterol, dietary fiber, vitamins, and minerals (Ross Products Division, Abbott Laboratories). Homogenates (two 50-mL aliquots) of the 7 full-day menus of the AAD and Step II SFD were analyzed at Covance Laboratories, Inc (Madison, WI) with standard AOAC procedures for protein, carbohydrate, total fat, fatty acids, cholesterol, and dietary fiber. The nutrient compositions of the experimental diets are shown in Table 1
.
|
Compliance
In addition to the 3-d run-in period, which was used to identify noncompliers, the importance of compliance was stressed throughout the study by the staff nutritionists. Study subjects were asked to voluntarily disqualify themselves from the study if they did not comply with the regimen. A log of food and beverage intake was maintained daily by the study participants and monitored daily by study personnel; a weekly monitoring form was maintained for each participant by study personnel. Any food or beverages eaten outside of the Metabolic Diet Study Center were recorded, including caffeine-containing and alcoholic beverages. Liquid-formula products consumed off-site were accounted for by the return of all empty cans.
Blood lipid analyses
All serum lipid and lipoprotein analyses were performed at The Mary Imogene Bassett Research Institute, Lipid Research Center (Cooperstown, NY). Blood samples were analyzed for total cholesterol, LDL cholesterol, triacylglycerol, HDL cholesterol, apolipoprotein B-100 (apo B), and apolipoprotein A-I (apo A-I). All lipid assays were performed on a Roche MIRA random-access automated analyzer (Roche Diagnostics, Rotkreuz, Switzerland) and all samples were analyzed together at the end of the study to minimize assay variation. Non-HDL particles were precipitated with dextran sulfate (molecular weight: 50000). Total and HDL cholesterol were assayed by using an automated enzymatic method (Roche cholesterol esterase/oxidase and peroxidase/4 amino-antipyrene detection system). Triacylglycerols were assayed by using an enzymatic method (lipase and glycerol kinase coupled with glycerol-1-phosphate oxidation; Sigma Chemical Co, St Louis). LDL-cholesterol concentrations were calculated by using the Friedewald equation (LDL cholesterol = total cholesterol HDL triacylglycerol/5) with cholesterol concentrations as mg/dL (17). Apo B and apo A-I were assayed by rate nephelometry with use of specific polyclonal antisera (Beckman Instruments, Fullerton, CA). The Mary Imogene Bassett Lipid Research Center laboratory is a Centers for Disease Control and Prevention (CDC) Certified Regional Reference Center for lipid analyses; bimonthly calibration was done by using reference materials designated by the CDC and the International Immunological Society.
Satiety assessment
Diets differing in total fat content and form (solid or liquid) may influence hunger and subjective sensations of satiety. Visual analogue scales (VAS) were used to assess hunger, thirst, nausea, prospective consumption (how much individuals thought they could eat), and fullness. VAS have been validated for use in investigating appetite (18, 19). For example, hunger was rated on a 100-mm line preceded by the question, "How hungry are you right now?" and anchored on the left by "not at all hungry" (0 mm) and on the right by "extremely hungry" (100 mm). Other anchors consisted of the phrases "not at all" and "extremely" in combination with the adjectives "thirsty," "nauseated," and "full." To assess feelings of satiety throughout the dietary conditions, VAS were completed on 3 different days (days 2, 12, and 23) during each diet period. On these days, subjects consumed breakfast, lunch, and dinner in the Metabolic Diet Study Center and completed ratings before and after lunch, at hourly intervals throughout the day, and before and after dinner. Quality of life questionnaires (20) were also administered on these days to assess mood, energy level, and overall wellness.
Statistical methods
All data were examined for normality by fitting a one-way, randomized block design analysis of variance (ANOVA) to the data and examining the residuals for normality. Normally distributed data were analyzed with a one-way randomized block ANOVA. If there were significant differences among the diet groups, Tukey's honestly significant difference test and contrast (food, dose, and interaction) were carried out to determine where the differences existed. Those variables (triacylglycerol and apo B) for which the residuals showed evidence of not being normally distributed (P < 0.05 with the Shapiro-Wilk test) were analyzed with nonparametric methods (Friedman's two-way ANOVA). Hourly ratings of hunger and satiety and mean daily values were analyzed by ANOVA using the general linear models procedure in which sex was tested as a between-subjects factor and condition (form of diet), fat intake, and time (day 2, 12, or 23) as withinsubjects factors. Tukey's honestly significant difference test was used for post hoc comparisons of significant effects with the appropriate error terms for between- and within-subjects factors specified. SAS software was used for the analysis (SAS Institute Inc, Cary, NC).
| RESULTS |
|---|
|
|
|---|
|
|
|
|
Effects of experimental diets on ratings of satiety
Ten men and 7 women provided data for this portion of the study. Overall, there were no consistent effects of time (day 2, 12, or 23) on any ratings; thus, mean values were calculated for each subject within each condition. Daily average ratings of hunger and prospective consumption did not differ significantly between diet forms (SFD compared with LFD) or fat intakes (Step II diet compared with AAD). The average daily ratings for hunger were 31 ± 3, 33 ± 3, 35 ± 4, and 32 ± 3 mm for the low-fat (Step II) and AAD LFD and the low-fat and AAD SFD, respectively. A significant effect of fat intake on average fullness rating was found for the SFD only (P < 0.04); however, the difference between conditions was not large (55 ± 4 and 50 ± 4 mm for the AAD and Step II SFD, respectively). Ratings of fullness for the LFD were 53 ± 4 mm for the AAD and 51 ± 3 mm for the Step II diet (NS). Ratings of nausea also differed by fat intake for the SFDs only (P < 0.02); these differences were small, however, and overall nausea ratings were low in all conditions (2 ± 1, 1 ± 0.5, 1 ± 0.5, and 3 ± 1 mm for the Step II diet and AAD LFD and Step II diet and AAD SFD, respectively). No significant differences were observed with respect to hunger, mood, energy level, or overall wellness assessed by the quality of life questionnaire. No systematic differences were found between men and women for any ratings.
| DISCUSSION |
|---|
|
|
|---|
Numerous studies using both solid food and liquid formulas conducted since the 1950s confirmed the potent hypercholesterolemic effects of SFAs (12:016:0) and dietary cholesterol (1). The results from the current study support the validity of the observations from well-controlled studies using LFDs and show that, given an appropriate experimental design in which similar diet forms are compared, LFDs can be used to assess the cholesterolemic response to changes in dietary lipids. In fact, the magnitude of the average effects on total cholesterol concentrations observed as a result of the changes in dietary fatty acid composition from either diet form were quantitatively similar to those estimated by the Keys et al (21) and Hegsted et al (22) predictive equations (Table 4
), which were developed from metabolic studies with SFDs. Note that the equations slightly underestimate the difference in the actual response between the AAD and Step II SFD by
0.23 mmol/L, whereas the difference between predicted and observed total cholesterol between the 2 LFDs was
0.09 mmol/L. The magnitude of these differences could be related to the consistency of intakes provided by the solid or liquid diet forms.
|
The present study, however, showed a significant effect of diet form on serum total cholesterol and triacylglycerol that appears to be independent of dietary fat composition. As shown in Table 4
, the Keys and Hegsted equations predict a negligible difference in total cholesterol (0.098 to 0.034 mmol/L for LFDs compared with SFDs) when considering only the small mean differences in fatty acids and cholesterol between diet forms; however, total cholesterol was elevated by 0.460.54 mmol/L when subjects consumed LFDs. The reasons for this independent effect of diet form on blood lipids are not known. Although an attempt was made to match the macronutrient compositions of the SFD and LFD as closely as possible, the 2 diet forms obviously differed in their physical characteristics. A complex whole-food diet varying in the proportion of nutrients delivered in meals and snacks, the texture of individual food components, and the presence of nonnutritive constituents (eg, fiber) and other naturally occurring phytochemicals can delay gastric emptying and prolong the absorption time of nutrients, whereas liquid diets made from purified ingredients are more rapidly emptied from the stomach (26). Some or all of these differences can affect fat digestion and absorption, lymphatic transport, bile acid metabolism, and postprandial responses of plasma lipoproteins (2729). For instance, viscous or fermentable fibers can interfere with the enterohepatic circulation of bile acids and increase their fecal excretion, which can increase hepatic conversion of cholesterol to bile acids and lower the hepatic cholesterol content, resulting in an increase in LDL-receptor activity and uptake of serum LDL cholesterol (30). These dietary fibers have well-documented cholesterol-lowering effects, which, in some cases, are equal in magnitude to those of fat (31). Although the carbohydrates in the experimental LFD were provided as a mixture of sources and included both soluble and insoluble fibers, the SFD provided a complex variety of carbohydrates. The efficiency of dietary cholesterol absorption can also be influenced by its physical form (32); the LFD provided primarily free cholesterol whereas a variable proportion (820%) of that in whole foods is esterified in adipose triacylglycerol or found as a structural component of cellular membranes. Thus, greater availability and absorption of cholesterol from the LFD may have contributed to some of the difference in blood lipids noted when the 2 diet forms were consumed.
Higher concentrations of triacylglycerol in subjects consuming LFDs also may be explained by their higher content of readily digestible carbohydrate than of the more complex carbohydrates in SFDs (33). The biological mechanism may be a result of the ability of insulin to stimulate VLDL and apo B production and secretion (34, 35). It is of interest that insulin also can stimulate b-hydroxy-b-methylglutaryl-CoA reductase activity (36), a rate-limiting step in cholesterol synthesis, which suggests another possible mechanism contributing to the higher total cholesterol concentrations in subjects consuming the LFD.
Finally, the present study also showed that there were no consistent differences between diets among the many subjective measures of satiety. An effect of fat intake on fullness was detected for the SFD only, although the difference was small, and no significant differences were found between ratings of hunger or prospective consumption. Note that the study subjects may not be representative of the general population because they agreed to consume a liquid diet for extended periods of time. Furthermore, it was not possible to determine the effects of energy density on satiety because subjects had unlimited access to non-energy-containing beverages and the diets were adjusted throughout the study to meet individual energy needs. Keep in mind, too, that LFDs may not be appropriate in many experimental study designs because the major disadvantage that limits their widespread use is that most people prefer eating solid foods. The lack of variety, chewing, and change in taste and texture with LFDs may be drawbacks to their use over extended periods of time. Despite these limitations, these data suggest that LFDs can be used in clinical settings without compromising subjective sensations of satiety, and thus limit feelings of deprivation and promote adherence to the experimental diet.
In conclusion, the results show that experimental diets that have a comparable nutrient profile but differ in physical form elicit a similar cholesterolemic response to changes in dietary total fat, SFAs, and cholesterol. Thus, because LFDs offer complete and balanced nutrition, adequate satiety, and safety and ease of administration, they greatly simplify the delivery of well-controlled experimental diets and can be used in clinical studies without compromising results.
| REFERENCES |
|---|
|
|
|---|
This article has been cited by other articles:
![]() |
C L. Kien, J. Y Bunn, and F. Ugrasbul Increasing dietary palmitic acid decreases fat oxidation and daily energy expenditure Am. J. Clinical Nutrition, August 1, 2005; 82(2): 320 - 326. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. H. Ledikwe, H. M. Blanck, L. K. Khan, M. K. Serdula, J. D. Seymour, B. C. Tohill, and B. J. Rolls Dietary Energy Density Determined by Eight Calculation Methods in a Nationally Representative United States Population J. Nutr., February 1, 2005; 135(2): 273 - 278. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. D. Ball, K. R. Keller, L. J. Moyer-Mileur, Y.-W. Ding, D. Donaldson, and W. D. Jackson Prolongation of Satiety After Low Versus Moderately High Glycemic Index Meals in Obese Adolescents Pediatrics, March 1, 2003; 111(3): 488 - 494. [Abstract] [Full Text] [PDF] |
||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |