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The Effect of a Plant-Based Diet on Plasma Lipids in Hypercholesterolemic Adults A Randomized Trial Christopher D. Gardner, PhD; Ann Coulston, MS, RD; Lorraine Chatterjee, MS; Alison Rigby, PhD, MPH, RD; Gene Spiller, PhD; and John W. Farquhar, MD Background: A variety of food combinations can be used to meet national U.S. guidelines for obtaining 30% of energy or less from total fat and 10% of energy or less from saturated fat. Objective: To contrast plasma lipid responses to 2 low-fat diet patterns. Design: Randomized clinical trial. Setting: 4-week outpatient feeding study with weight held con- stant. Participants: 120 adults 30 to 65 years of age with prestudy low-density lipoprotein (LDL) cholesterol concentrations of 3.3 to 4.8 mmol/L (130 to 190 mg/dL), body mass index less than 31 kg/m 2 , estimated dietary saturated fat at least 10% of calories, and otherwise general good health. Measurements: Plasma lipid levels. Intervention: Two diets, the Low-Fat diet and the Low-Fat Plus diet, designed to be identical in total fat, saturated fat, protein, carbohydrate, and cholesterol content, consistent with former American Heart Association Step I guidelines. The Low-Fat diet was relatively typical of a low-fat U.S. diet. The Low-Fat Plus diet incorporated considerably more vegetables, legumes, and whole grains, consistent with the 2000 American Heart Association re- vised guidelines. Results: Four-week changes in the Low-Fat and Low-Fat Plus groups were 0.24 mmol/L (9.2 mg/dL) versus 0.46 mmol/L (17.6 mg/dL) for total cholesterol (P 0.01) and 0.18 mmol/L (7.0 mg/dL) versus 0.36 mmol/L (13.8 mg/dL) for LDL cholesterol (P 0.02); between-group differences were 0.22 mmol/L (9 mg/dL) (95% CI, 0.05 to 0.39 mmol/L [2 to 15 mg/dL]) and 0.18 mmol/L (7 mg/dL) (CI, 0.04 to 0.32 mmol/L [2 to 12 mg/dL]) for total and LDL cholesterol, respectively. The 2 diet groups did not differ significantly in high- density lipoprotein cholesterol and triglyceride levels. Limitations: 4-week duration. Conclusions: Previous national dietary guidelines primarily em- phasized avoiding saturated fat and cholesterol; as a result, the guidelines probably underestimated the potential LDL cholesterol– lowering effect of diet. In this study, emphasis on including nu- trient-dense plant-based foods, consistent with recently revised national guidelines, increased the total and LDL cholesterol–low- ering effect of a low-fat diet. Ann Intern Med. 2005;142:725-733. www.annals.org For author affiliations, see end of text. I t is well established that elevated low-density lipoprotein (LDL) cholesterol concentrations are a risk factor for car- diovascular diseases and that dietary modification is con- sidered a first approach to their treatment and control (1, 2). For several decades, dietary modification for lipid management traditionally focused on avoiding saturated fat and cholesterol (3–5). Previous examples of dietary in- terventions targeting LDL cholesterol level often reported only modest lipid improvements, leading some to consider diet a relatively ineffective therapy (6). However, recent developments have suggested that the traditional focus of lipid management may have been overly simplistic and that diets might be more effective if more attention was focused on including certain foods or factors rather than just avoid- ing saturated fat and cholesterol. Effective refinements of dietary strategies for lipid management could decrease the gap in effectiveness between dietary approaches and drug therapy. Several dietary factors or foods, including soy protein, soy isoflavones, plant sterols, soluble fiber, oats, nuts, and garlic, have established or potential lipid benefits (7–13). Each is derived from plant food sources, and it is inclusion of these factors, rather than avoidance, that is reported to confer benefits. However, given that most plant foods con- tain low or negligible amounts of saturated fat and that all plant foods are devoid of cholesterol, it follows that a plant-based diet is inherently low in saturated fat and cho- lesterol. Therefore, it is difficult to distinguish between plasma lipid benefits derived from the actual plant-based dietary components and those derived from avoidance of saturated fat and cholesterol. Several studies have been designed to test the effects on plasma lipids of diets with identical saturated fat and cholesterol intake but varied amounts of 1 or 2 additional dietary components (14 –16). Data are more limited on dietary approaches that hold saturated fat and cholesterol See also: Print Editors’ Notes ............................. 726 Editorial comment.......................... 793 Summary for Patients ....................... I-35 Web-Only Appendix Tables Conversion of figures and tables into slides Annals of Internal Medicine Article © 2005 American College of Physicians 725

The Effect of a Plant-Based Diet on Plasma Lipids

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The Effect of a Plant-Based Diet on Plasma Lipids inHypercholesterolemic AdultsA Randomized TrialChristopher D. Gardner, PhD; Ann Coulston, MS, RD; Lorraine Chatterjee, MS; Alison Rigby, PhD, MPH, RD; Gene Spiller, PhD; andJohn W. Farquhar, MD

Background: A variety of food combinations can be used tomeet national U.S. guidelines for obtaining 30% of energy or lessfrom total fat and 10% of energy or less from saturated fat.

Objective: To contrast plasma lipid responses to 2 low-fat dietpatterns.

Design: Randomized clinical trial.

Setting: 4-week outpatient feeding study with weight held con-stant.

Participants: 120 adults 30 to 65 years of age with prestudylow-density lipoprotein (LDL) cholesterol concentrations of 3.3 to4.8 mmol/L (130 to 190 mg/dL), body mass index less than 31kg/m2, estimated dietary saturated fat at least 10% of calories,and otherwise general good health.

Measurements: Plasma lipid levels.

Intervention: Two diets, the Low-Fat diet and the Low-Fat Plusdiet, designed to be identical in total fat, saturated fat, protein,carbohydrate, and cholesterol content, consistent with formerAmerican Heart Association Step I guidelines. The Low-Fat dietwas relatively typical of a low-fat U.S. diet. The Low-Fat Plus dietincorporated considerably more vegetables, legumes, and whole

grains, consistent with the 2000 American Heart Association re-vised guidelines.

Results: Four-week changes in the Low-Fat and Low-Fat Plusgroups were �0.24 mmol/L (�9.2 mg/dL) versus �0.46 mmol/L(�17.6 mg/dL) for total cholesterol (P � 0.01) and �0.18 mmol/L(�7.0 mg/dL) versus �0.36 mmol/L (�13.8 mg/dL) for LDLcholesterol (P � 0.02); between-group differences were �0.22mmol/L (�9 mg/dL) (95% CI, �0.05 to �0.39 mmol/L [�2 to�15 mg/dL]) and �0.18 mmol/L (�7 mg/dL) (CI, �0.04 to�0.32 mmol/L [�2 to �12 mg/dL]) for total and LDL cholesterol,respectively. The 2 diet groups did not differ significantly in high-density lipoprotein cholesterol and triglyceride levels.

Limitations: 4-week duration.

Conclusions: Previous national dietary guidelines primarily em-phasized avoiding saturated fat and cholesterol; as a result, theguidelines probably underestimated the potential LDL cholesterol–lowering effect of diet. In this study, emphasis on including nu-trient-dense plant-based foods, consistent with recently revisednational guidelines, increased the total and LDL cholesterol–low-ering effect of a low-fat diet.

Ann Intern Med. 2005;142:725-733. www.annals.orgFor author affiliations, see end of text.

It is well established that elevated low-density lipoprotein(LDL) cholesterol concentrations are a risk factor for car-

diovascular diseases and that dietary modification is con-sidered a first approach to their treatment and control(1, 2). For several decades, dietary modification for lipidmanagement traditionally focused on avoiding saturatedfat and cholesterol (3–5). Previous examples of dietary in-terventions targeting LDL cholesterol level often reportedonly modest lipid improvements, leading some to considerdiet a relatively ineffective therapy (6). However, recentdevelopments have suggested that the traditional focus oflipid management may have been overly simplistic and thatdiets might be more effective if more attention was focusedon including certain foods or factors rather than just avoid-ing saturated fat and cholesterol. Effective refinements ofdietary strategies for lipid management could decrease thegap in effectiveness between dietary approaches and drugtherapy.

Several dietary factors or foods, including soy protein,soy isoflavones, plant sterols, soluble fiber, oats, nuts, andgarlic, have established or potential lipid benefits (7–13).Each is derived from plant food sources, and it is inclusionof these factors, rather than avoidance, that is reported toconfer benefits. However, given that most plant foods con-

tain low or negligible amounts of saturated fat and that allplant foods are devoid of cholesterol, it follows that aplant-based diet is inherently low in saturated fat and cho-lesterol. Therefore, it is difficult to distinguish betweenplasma lipid benefits derived from the actual plant-baseddietary components and those derived from avoidance ofsaturated fat and cholesterol.

Several studies have been designed to test the effectson plasma lipids of diets with identical saturated fat andcholesterol intake but varied amounts of 1 or 2 additionaldietary components (14–16). Data are more limited ondietary approaches that hold saturated fat and cholesterol

See also:

PrintEditors’ Notes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 726Editorial comment. . . . . . . . . . . . . . . . . . . . . . . . . . 793Summary for Patients. . . . . . . . . . . . . . . . . . . . . . . I-35

Web-OnlyAppendix TablesConversion of figures and tables into slides

Annals of Internal Medicine Article

© 2005 American College of Physicians 725

Page 2: The Effect of a Plant-Based Diet on Plasma Lipids

intake constant while modifying multiple other dietarycomponents simultaneously (17). Modifying multiple di-etary components simultaneously (for example, increasingintake of vegetables, fruits, and low-fat dairy) while hold-ing sodium intake constant has been shown to effectivelylower elevated blood pressure in the Dietary Approaches toStop Hypertension trials (DASH I and II) (18, 19). Test-ing a parallel approach to refining dietary intervention forlipid management is warranted.

In 2000, the American Heart Association (AHA) re-ported revised dietary guidelines that substantially modi-fied its 1993 and 1996 guidelines (2, 4, 5). All 3 versions ofthe guidelines recommended keeping saturated fat intakeat less than 10% of energy and cholesterol intake below300 mg/d. A notable modification of the 2000 guidelineswas to emphasize foods and overall eating patterns, includ-ing increased intakes of vegetables and whole grains (ingeneral, a plant-based diet). It was our hypothesis that aplant-based diet consistent with the revised AHA 2000guidelines would increase the LDL cholesterol–loweringbenefits of the previous AHA Step I guidelines. We theo-rized that this improvement would be independent of theplant-based diet’s saturated fat and cholesterol content.Therefore, we designed 2 diets that had identical levels oftotal fat (30% of energy), saturated fat (10% of energy),and cholesterol (�300 mg/d) but differed substantially incontent of nutrient- and phytochemical-dense plant-basedfoods. The purpose of the study was to determine whetherLDL cholesterol–lowering benefits among adults withmoderately elevated cholesterol levels would be greater un-der weight-stable conditions with a plant-based low-fat dietthan with a more typical, convenience-oriented low-fat diet

that was identical in intake of total fat, saturated fat, andcholesterol.

METHODS

ParticipantsParticipants were recruited from the local community,

primarily through newspaper advertisements, letters to pre-vious study participants, and flyers sent to university em-ployees. Men and women were invited to enroll if theywere 30 to 65 years of age with fasting plasma LDL cho-lesterol levels of 3.3 to 4.8 mmol/L (130 to 190 mg/dL),fasting plasma triglyceride levels less than 2.83 mmol/L(� 250 mg/dL), body mass index between 19 and 31 kg/m2, and a current diet estimated to derive at least 10% ofenergy from saturated fat. Pregnant women, persons whosmoked, persons with prevalent heart disease or diabetes,or persons who had been using lipid-lowering or bloodpressure–lowering medications within the past month (alldetermined through self-report) were excluded. During therecruitment phase, 1096 individuals were screened by tele-phone interview and 345 who met the initial inclusioncriteria were considered eligible for cholesterol testing. Ofthese 345 persons, 188 who were found to have eligibleconcentrations of LDL cholesterol and triglycerides at-tended an orientation meeting. Fifty-one persons decidednot to participate (primarily because of the time commit-ment), and an additional 12 potential participants wereexcluded after a 3-day food record showed that their esti-mated average intake of saturated fat was already less than10% of energy. One hundred twenty-five participants wererandomly assigned to 1 of the 2 diet groups. The StanfordUniversity Human Subjects Committee reviewed andapproved the investigation, all participants signed aninformed consent form before enrollment, and the studywas performed according to Declaration of Helsinki guide-lines (20).

DesignThe trial used a parallel design. We randomly assigned

participants in blocks of 20 by selecting, without replace-ment, from a set of indistinguishable envelopes containing10 assignments to each of the 2 diet groups. Randomiza-tion of the envelopes was done by hand, without a com-puter algorithm. No stratification criteria were used. Eachparticipant was provided with meals, snacks, and beverageson an outpatient basis for 28 days, as described later.

DietsBoth study diets were designed to provide 30% of

energy from total fat, 10% of energy from saturated fat,and approximately 100 mg of cholesterol per 1000 kcal perday. During the menu-designing stage of the study, thenutrient composition of the diets was determined by usingthe database of Food Processor software, version 7.0(ESHA Research, Salem, Oregon). Menus were designedby using commonly available foods from local markets.

Context

People can achieve recommended fat intake while con-suming high or low amounts of vegetables, fruits,legumes, and whole grains.

Contribution

This 4-week randomized trial compared 2 diets with differ-ent vegetable, fruit, legume, and whole-grain content butidentical total fat, saturated fat, protein, carbohydrate, andcholesterol content. The 59 adults who consumed highamounts of vegetables, fruits, legumes, and whole grainshad greater improvements in total and low-densitylipoprotein cholesterol levels than the 61 adults who atelow amounts of these foods.

Implications

At least over the short term, greater improvements in low-density lipoprotein and total cholesterol are an additionalbenefit of diets high in vegetables, fruits, legumes, andwhole grains.

–The Editors

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The Low-Fat diet was designed to include many reduced-fat prepared-food items (for example, reduced-fat cheeses,low-fat frozen lasagna, and low-fat and sugar-rich snackfoods). In contrast, the Low-Fat Plus diet was designed toinclude considerably more vegetables, legumes, wholegrains, and fruits. Butter, cheese, and eggs were added tothe daily menus for the Low-Fat Plus diet, increasing thesaturated fat and cholesterol content to match the Low-Fatdiet.

A 7-day menu cycle was designed for each of the 2study diets; therefore, each menu was repeated 4 timesduring the 28 days. The diets included breakfast, lunch,dinner, beverages, and snacks for each day. Each weekday,the participants ate either lunch or dinner at the diningfacility of the Stanford General Clinical Research Center.After their on-site meal, they were given coolers that con-tained meals and snacks to be consumed off-site. On Fri-days, participants received weekend meals to be consumedoff-site. Appendix Table 1 and Appendix Table 2 (avail-able at www.annals.org) list the daily menus.

One “free-choice” evening meal was allowed eachweekend. For this meal, participants were given guidelinesfor choosing low-fat meals consistent with their diet assign-ments and were required to keep a record of foods con-sumed. These records were analyzed for nutritional contentand were used to determine the impact of the free-choicemeals on the overall study diets.

Adherence was measured by using daily log sheets keptby participants that tracked incomplete consumption ofstudy foods or consumption of any nonstudy foods. The28 daily food logs for each participant were examined fordeviations from the diets. The energy contribution of eachdeviation was determined and then totaled for the entire28-day protocol period.

Each of the 14 daily menus (7-day cycle � 2 diets)was analyzed chemically for nutrient content before thestudy and then again during the study (Covance Labora-tories, Madison, Wisconsin). The chemical analyses per-formed before the study confirmed that the average com-position of the daily menus provided 30% of energy fromtotal fat, 10% of energy from saturated fat, and approxi-mately 100 mg of cholesterol per 1000 kcal per day.

When the 2 diets were first designed, we attempted tomatch their mono- and polyunsaturated fat content. How-ever, the database used in the design phase was missingvalues for these nutrients for approximately 20% of thefoods. In addition, many of the specific products purchasedlocally for the study provided incomplete information forthe content of these unsaturated fats. The first round ofchemical analyses of the diets, performed before enroll-ment began, indicated a modest discrepancy betweenmonounsaturated and polyunsaturated fat. We made mi-nor modifications to 3 of the daily menus to address thisdiscrepancy (for example, by substituting the types of veg-etable oils used in menu preparation). Unexpectedly, de-spite these modifications, the on-study chemical analyses

revealed even larger discrepancies in monounsaturated andpolyunsaturated fat than the prestudy analyses. However,as several meta-analyses have shown, the effect of this levelof difference in monounsaturated versus polyunsaturatedfat intake on serum lipids would be considered negligible(21, 22).

Soy protein and fresh garlic were not used in themenus for the Low-Fat diet, with the exception of onequarter of a teaspoon of dried garlic spice in 1 menu itemon 1 day of the week. In contrast, soy protein and freshgarlic were used daily in the Low-Fat Plus diet. Mean dailyintake of soy protein (�SD) was 16.2 � 9.9 g/2000 kcal,and mean daily intake of garlic (�SD) was 1.4 � 0.7cloves/2000 kcal. The daily menus were originally designedto contain 2000 kcal/d and were then proportionally mod-ified at 3 additional levels: 1800, 2600, and 3000 kcal/d.We also developed muffins for each of the 2 diet groupsthat contained 200 kcal/d and had the same macronutrientcontent as the full diets.

Each participant was weighed every weekday. Weightwas kept stable by changing energy intake in increments of200 kcal/d whenever a change of 0.5 kg was observed andsustained for at least 2 days.

Data CollectionThe baseline weight was established as the average

weight on the first 3 weekdays of the study diet, and theend-study weight was determined as the average weight onthe last 3 weekdays of the study diet. The Stanford 7-dayphysical activity recall questionnaire was administered onthe first and last day of the 28-day study period (23).

On 4 separate days, 2 at baseline and 2 at the end ofthe study, fasting blood samples were collected in EDTAtubes by using venipuncture and were refrigerated imme-diately. Plasma samples were stored in Wheaton vials andwere frozen at �70o C until a given participant had com-pleted the protocol. After protocol completion, a set ofsamples for each participant was thawed and analyzed in asingle batch to minimize laboratory variability. Plasma to-tal cholesterol level and triglyceride level (with subtractionof a free glycerol blank) were measured by enzymatic pro-cedures using established methods of the Lipid ResearchClinics (ABA 200 instrument, Abbott Laboratories, AbbottPark, Illinois) (24, 25). High-density lipoprotein (HDL)cholesterol level was measured by using dextran sulfate–magnesium precipitation (26) followed by enzymatic de-termination of cholesterol (24). Low-density lipoproteincholesterol level was calculated according to the method ofFriedewald and associates (27). Lipid assays were moni-tored by using the Lipid Standardization Program of theCenters for Disease Control and Prevention and the Na-tional Heart, Lung, and Blood Institute and were consis-tently within specified limits (monthly coefficients of vari-ation were �2.8%).

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Statistical AnalysisThe primary hypothesis, stated as the null, was that

the 4-week change in LDL cholesterol concentrationwould not differ between the 2 diets. Sample size (n � 60for each group) was estimated to allow 80% power to de-tect a between-group difference of 0.26 mmol/L (10 mg/dL) in LDL cholesterol level as significant, assuming anestimated standard deviation of 0.52 mmol/L (20 mg/dL)for change and a 2-sided � value of 0.05. Statistical testswere performed by using SAS, version 8.02 (SAS InstituteInc., Cary, North Carolina). Descriptive statistics usingmeans and standard deviations were determined for thebaseline characteristics of the participants. Differences inbaseline characteristics and in 4-week changes in weightand physical activity between the 2 groups were examinedby using analysis of covariance, adjusting for sex. Four-week changes in plasma lipid levels were compared by dietgroup by using an analysis of covariance model with thebaseline value included as a covariate. For this analysis, theaverage of the 2 baseline measurements was used as the

baseline value and the average of the two 4-week measure-ments was used as the final value. Sex, baseline weight andphysical activity, and changes in weight and physical activ-ity were considered as additional covariates in these mod-els; however, they did not contribute significantly andtherefore were not included in the final models. All statis-tical tests were 2-tailed, and the significance level was 0.05.

Role of the Funding SourcesThis study was supported by the National Heart,

Lung, and Blood Institute and by General Clinical Re-search Centers, National Center for Research Resources,National Institutes of Health. Other than reviewing theinitial grant proposal and protocol, the funding sourceshad no role in the design, conduct, or reporting of thestudy or in the decision to submit the manuscript for pub-lication.

RESULTS

Matched and Unmatched Dietary ComponentsThe study diets were closely matched in energy and

the primary nutrients of interest: total fat, saturated fat,cholesterol, and the percentage of energy from protein andcarbohydrate. The indirect database analyses and the directchemical analyses were in good agreement, as shown inTable 1. The amounts of a selected set of other nutrientsthat were left unmatched by design are also presented inTable 1. In some cases, these values were available onlythrough one method of assessment, not both. For example,plant sterol content was determined only by chemical anal-ysis, and soluble fiber data were available for most foods inthe database but were often below the level of detection inthe mixed meal slurries provided for chemical analyses.Compared with the Low-Fat diet, the Low-Fat Plus dietwas higher in fiber, �-carotene, vitamin C, vitamin E, fo-late, and �-sitosterol. Sodium content of the 2 diets wassimilar according to the electronic database’s calculationsbut was approximately 20% higher in the Low-Fat dietaccording to chemical analyses. Table 2 shows the averagenumber of servings of selected food groups per day. TheLow-Fat Plus diet contained more servings of whole grains;vegetables; fruits; and beans, legumes, nuts, and seeds.

Table 1. Nutrient Composition of Study Diets per 2000 kcal

Variable Low-Fat Diet Low-Fat Plus Diet

Database* ChemicalAnalysis†

Database* ChemicalAnalysis†

Matched by designFat, % of energy 30.4 29.8 31.0 31.7Saturated fat, % of

energy10.1 9.5 10.1 9.5

Carbohydrate, % ofenergy

55.0 55.6 56.4 54.1

Protein, % ofenergy

15.3 14.6 15.4 14.1

Cholesterol, mg 190 187‡ 210 200

UnmatchedMonounsaturated

fat, %§10.9 9.2 9.3 9.4

Polyunsaturated fat,%§

6.7 6.4 7.6 9

Fiber, g 13.9 22.0� 48.0 40.8Soluble¶ 3.2 8.3Insoluble¶ 5.9 13.9

�-Sitosterol, mg** 120 175�-Carotene, �g 470 810 11 930 16 030Vitamin C, mg 65 72‡ 233 123Vitamin E, IU¶ 6.5 21.0Folate, �g 244 430 486 509Sodium, mg 2365 2845 2330 2315

* Average of 7-day menus as designed by using the Food Processor nutrient data-base (ESHA Research, Salem, Oregon).† Average of 7-day menus determined by chemical analyses (Covance Laboratories,Madison, Wisconsin), once for each on-study menu.‡ Values available for 6 of the 7 menus; 1 of the 7 values was below the level ofdetection sensitivity.§ Monounsaturated and polyunsaturated fat values were unavailable for approxi-mately 20% of the foods in the ESHA database used to design the menus. See thetext for more details.� On 3 of the 7 days of the Low-Fat diet, the amount of fiber was determined tobe below the level of detection sensitivity (1.0 g per 100 g of meal slurry). Forthose 3 days, imputed values of 0.9 g of fiber per 100 g of meal slurry were usedto calculate the average, which may have been an overestimate.¶ Levels were below the level of detection sensitivity in the chemical analyses andare not reported.** Levels were not available in the Food Processor nutrient database.

Table 2. Comparison of Mean Number of Servings of FoodGroups per Day in the 2 Diets*

Variable Servings inLow-FatGroup, n

Servings inLow-Fat PlusGroup, n

Grains 7.0 � 2.1 4.5 � 2.3Whole grains 0 � 0 3.5 � 1.8

Vegetables 2.5 � 1.2 10.1 � 2.7Fruit 2.6 � 1.2 3.4 � 1.3Beans, legumes, nuts, and seeds 0.3 � 0.8 4.0 � 1.6Milk, yogurt, and cheese 1.5 � 1.6 1.4 � 0.7Beef, poultry, fish, and eggs 1.9 � 0.7 0.8 � 0.2

* Values are means � SD, based on 7-day menus of 2000 kcal/d.

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Retention, Adherence, Free-Choice Meals, and WeightStability

Of the 125 adults randomly assigned to a diet, 120completed the protocol. Two participants, 1 in each of the2 diet groups, dropped out because they strongly dislikedtheir diet assignments. One participant in the Low-Fatgroup dropped out after reporting difficulties toleratingdairy products. Another participant in the Low-Fat groupwhose documentation indicated poor adherence was askedto improve adherence but instead chose to drop out. Thefinal participant dropped out immediately after randomiza-tion (and before starting the study diet) because of extremedifficulties with the baseline blood sampling. Baseline char-acteristics of the 120 participants with complete data weresimilar between the 2 groups (Table 3).

Quantitative assessment of diet adherence was deter-mined from daily log sheets kept by participants. Over the28-day period, the average deviation from the study mealsreported by participants (that is, nonstudy foods consumedor study foods not entirely consumed) was less than 1% forboth groups.

Participants were required to keep records of theirweekly “free-choice” meals, which were subsequently ana-lyzed for nutrient content. The mean energy content ofthese meals (�SD) was 890 � 410 kcal and 840 � 405kcal for the Low-Fat and Low-Fat Plus groups, respec-

tively, representing approximately 5% of participants’ en-ergy intake over the entire 28-day period. The mean satu-rated fat content of these meals was almost identical to thatof the controlled meals (10.5% and 9.6% energy for theLow-Fat and Low-Fat Plus groups, respectively). There-fore, the impact of these once-per-week free-choice mealswas considered to be consistent with, and to have a negli-gible impact on, the controlled 20 meals per week (7breakfasts, 7 lunches, and 6 dinners) and the daily snacksthat contributed 95% of energy intake.

Mean weight changes (�SD) were negligible and didnot differ significantly between the 2 groups over the 28-day period (�0.5 � 0.6 kg for the Low-Fat group and�0.7 � 0.7 kg for the Low-Fat Plus group). There wereno significant differences in mean changes in activity level(�SD) within or between groups from the week immedi-ately preceding enrollment to the final week of the feedingstudy (0.1 � 4.2 kcal/kg per day for the Low-Fat groupand �0.6 � 2.3 kcal/kg per day for the Low-Fat Plusgroup) (P � 0.2).

LipidsFigure 1 shows 4-week changes in plasma lipid levels.

Regarding missing data for the 120 participants who com-pleted the entire 4-week protocol, 2 participants missed 1of the 2 baseline blood draws and 3 participants missed 1

Table 3. Baseline Characteristics*

Characteristic Women (n � 60) Men (n � 60) All (n � 120)

Low-Fat Group(n � 27)

Low-Fat Plus Group(n � 33)

Low-Fat Group(n � 34)

Low-Fat Plus Group(n � 26)

Low-Fat Group(n � 61)

Low-Fat Plus Group(n � 59)

DemographicAge, y 46 � 9 48 � 7 49 � 11 48 � 12 48 � 10 49 � 8BMI, kg/m2 26 � 2 25 � 3 28 � 3 27 � 3 27 � 3 26 � 3Education, y 16 � 2 16 � 2 17 � 2 17 � 1 16 � 2 16 � 2Daily physical

activity,kcal/kg

34 � 2 35 � 2 36 � 4 35 � 2 35 � 3 35 � 2

Non-Hispanicwhiteethnicity, %

81 82 68 69 75 76

DietFat, % of energy 35 � 7 36 � 7 37 � 6 38 � 6 36 � 7 37 � 6Saturated fat, %

of energy13 � 4 13 � 3 13 � 3 13 � 3 13 � 3 13 � 3

Carbohydrate, %of energy

50 � 6 48 � 7 46 � 7 45 � 9 48 � 6 47 � 8

Protein, % ofenergy

15 � 3 16 � 2 16 � 5 15 � 3 16 � 4 15 � 3

Cholesterol,mg/d

327 � 181 294 � 171 354 � 147 351 � 134 340 � 170 315 � 155

Fiber, g/d 21 � 6 19 � 7 21 � 8 24 � 10 21 � 7 21 � 9

Lipid levels,mmol/L (mg/dL)

Total cholesterol 6.0 � 0.8 (231 � 31) 5.8 � 0.6 (224 � 22) 5.6 � 0.7 (217 � 28) 5.7 � 0.6 (219 � 22) 5.8 � 0.8 (223 � 30) 5.8 � 0.6 (222 � 22)LDL cholesterol 3.9 � 0.6 (150 � 22) 3.9 � 0.6 (149 � 22) 3.9 � 0.6 (150 � 25) 3.8 � 0.4 (146 � 17) 3.9 � 0.6 (150 � 23) 3.8 � 0.5 (148 � 20)HDL cholesterol 1.4 � 0.3 (54 � 13) 1.4 � 0.4 (55 � 15) 1.0 � 0.2 (39 � 7) 1.1 � 0.3 (44 � 13) 1.2 � 0.3 (45 � 12) 1.3 � 0.4 (50 � 15)Triglyceride 1.5 � 0.8 (134 � 67) 1.2 � 0.5 (103 � 45) 1.5 � 0.6 (137 � 52) 1.6 � 0.9 (145 � 81) 1.5 � 0.7 (135 � 58) 1.4 � 0.7 (121 � 66)

* Values presented with a plus/minus sign are means � SD. BMI � body mass index; HDL � high-density lipoprotein; LDL � low-density lipoprotein.

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of the 2 end-study blood draws. No participants missedboth a baseline and an end-study blood draw. In the anal-yses, the single measurements for these 5 data points wereused in place of the average of the intended 2 measure-ments. The changes in total cholesterol concentrations forthe Low-Fat and Low-Fat Plus groups were �0.24mmol/L (�9.2 mg/dL) and �0.46 mmol/L (�17.6 mg/dL), respectively, and the between-group difference was�0.22 mmol/L (�9 mg/dL) (95% CI, �0.05 to �0.39mmol/L [�2 to �15 mg/dL]). For levels of LDL choles-terol, HDL cholesterol, and triglycerides, the changes were�0.18 mmol/L (�7 mg/dL) versus �0.36 mmol/L(�13.8 mg/dL), �0.06 mmol/L (�2.5 mg/dL) versus�0.10 mmol/L (�3.8 mg/dL), and 0.01 mmol/L (1.2 mg/dL) versus 0.00 mmol/L (0.1 mg/dL), respectively, for theLow-Fat and Low-Fat Plus groups. Respective between-group differences were �0.18 mmol/L (�7 mg/dL) (CI,�0.04 to �0.32 mmol/L [�2 to �12 mg/dL]), �0.04mmol/L (�2 mg/dL) (CI, 0.01 to �0.08 mmol/L [0.4 to�3 mg/dL]), and 0.01 mmol/L (0.9 mg/dL) (CI, 0.38 to�0.44 mmol/L [34 to �39 mg/dL]). Only the changes intotal cholesterol and LDL cholesterol levels differed signif-icantly between groups (P � 0.014 and P � 0.016, respec-tively). There were no significant changes within or be-tween the Low-Fat and Low-Fat Plus groups in the ratio oftotal cholesterol to HDL cholesterol (0.1 [CI, �0.13 to0.15] vs. �0.02 [CI, �0.16 to 0.12]).

Given the possibility of bias due to informative dropout,we conducted sensitivity analyses to examine the robustness ofour findings. We assigned a large LDL cholesterol–loweringresponse (the average of the top 10% of responders in theLow-Fat group) to the 3 participants who started but did notcomplete the Low-Fat arm and a large increase in LDL

cholesterol response (the average of the worst 10% of respond-ers in the Low-Fat Plus group) to the single participant whostarted but did not complete the Low-Fat Plus arm. Thisrelatively extreme scenario changed the significance level forLDL cholesterol from a P value of 0.016 to a P value of 0.068and changed the effect size from 0.32 to 0.24. Conversely,imputing large responses in the opposite direction for the 4participants with missing end-study data (that is, favoring thebetter response in the Low-Fat Plus group) changed the sig-nificance level for LDL cholesterol level to a P value of 0.0036and the effect size to 0.38. Given this narrow range of effectsizes under these unlikely and relatively extreme assumptionsfor 4 of 124 participants who had baseline data but no end-study data, the findings for the main study outcome are notsensitive to the 4 missing data points. Similar imputations fortotal cholesterol, HDL cholesterol, and triglycerides alsoyielded negligible changes in effect sizes.

The individual participant results for 4-week change inLDL cholesterol level are presented in Figure 2, whichdemonstrates the substantial individual variation in re-sponse to dietary change. Proportions of participants withdecreases in LDL cholesterol level were similar in the 2 dietgroups, but decreases were generally greater in the Low-FatPlus group. No sex effects were observed in ancillary anal-yses (P � 0.2); in other words, there was no statisticallysignificant interaction between sex and diet as determinedby the general linear model, although the study was notpowered to examine the results separately by sex.

DISCUSSION

In this randomized clinical trial, we observed a signif-icantly greater reduction in total and LDL cholesterol lev-els among moderately hypercholesterolemic men and

Figure 1. Mean 4-week changes (±SE) in plasma lipid and lipoprotein levels.

The data presented are least-squares means adjusted individually for baseline concentrations of each variable. The 4-week changes from baseline in totalcholesterol concentrations for the Low-Fat (n � 61) and Low-Fat Plus (n � 59) groups were �4.1% and �7.9%, respectively (P � 0.014). Similarly,the changes were �4.6% and �9.3% for low-density lipoprotein (LDL) cholesterol (P � 0.016), �5.5% and �7.7% for high-density lipoprotein(HDL) cholesterol (P � 0.13), and 0.9% and 0.1% for triglycerides (P � 0.2).

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women who consumed the plant-based low-fat diet com-pared with those who consumed the more convenience-food–based low-fat diet. This differential effect on LDLcholesterol concentrations is probably attributable to atleast 1 and probably a combination of the components thatdiffered in the 2 diets, such as the higher content of soy,fiber, garlic, and plant sterols in the Low-Fat Plus diet andpossibly other unmeasured differences. However, the studywas not designed to determine which of these componentswere responsible for the effect observed. Rather, the study’spurpose was to compare the impact of 2 dietary patternson LDL cholesterol level and other plasma lipid concentra-tions. The results clearly demonstrate that the differenceswere not attributable to saturated fat, cholesterol, energyintake, or body weight, because each of these variables wassimilar and constant in the 2 diet groups by design.

An inherent complexity of most nutrition studies in-volving food intake is that the addition of a food item tothe diet typically involves replacing another food item.This makes it difficult to determine whether changedhealth outcomes are attributable to the presence or omis-sion of the item or to a combination of these influences.The inverse correlation between plant-based food intakeand saturated fat intake provides an example; increasingintake of plant-based foods that are typically low in satu-rated fat usually involves replacing other foods that arehigher in saturated fat and subsequently reduces saturatedfat intake. Our study was designed to address this inter-relationship by adding butter, cheese, and eggs to theplant-based diet to match the saturated fat and cholesterolcontent of the comparison diet while leaving many otherplant-based components unmatched.

Although the overall changes in total and LDL choles-terol level were greater in the Low-Fat Plus group on av-erage, the presentation of individual LDL cholesterol re-

sponses in Figure 2 demonstrates the wide range ofvariability of response. This is often the case in interven-tion trials designed to affect plasma lipid concentrationsand reflects not only the variability in response to the in-tervention but also other sources of potential variability(for example, day-to-day individual variability, minorvariability in blood sampling, and laboratory variability)(28, 29).

Our trial focused on LDL cholesterol levels, but wealso obtained and presented results for HDL cholesterollevels, which decreased slightly in both diet groups. Thisdecrease, although not statistically significant betweengroups, contributed to the lack of a significant between-group difference in the ratio of total cholesterol to HDLcholesterol. Dietary interventions that lower total and LDLcholesterol levels also often lower HDL cholesterol levels(16, 30). Whether a decrease in HDL cholesterol level thatcoincides with a decrease in total and LDL cholesterol lev-els would be considered detrimental remains a matter ofdebate. It may depend on whether certain subfractions ofHDL cholesterol were more or less affected than others, anissue not assessed in this study (16, 31). Triglyceride con-centrations did not change in either group.

Studies investigating dietary patterns and those inves-tigating isolated nutrients have important differences.There are advantages to the dietary pattern approach fromboth a research perspective and from a practical, publichealth perspective. One scientific advantage is the possibil-ity of observing the potential additive or synergistic effectsof combining different dietary components (14, 17–19,32). A practical advantage to studying dietary patterns ver-sus isolated nutrient manipulations is that the former aremore relevant to the ways people choose their foods (forexample, following a plant-based diet or a Mediterraneandiet vs. increasing dietary fiber).

Figure 2. Raw data for 4-week changes in low-density lipoprotein (LDL) cholesterol level of individual study participants.

Each bar represents the result of a single participant, and the results have been sorted from largest decrease to largest increase from left to right, for eachgroup.

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Although the intent of our study was to focus on adietary pattern, several components of the Low-Fat Plusdiet were included specifically because of their establishedor potential cholesterol-lowering effects. These dietarycomponents included soy protein (approximately 16g/2000 kcal in the Low-Fat Plus diet vs. 0 g/2000 kcal inthe Low-Fat diet), dietary fiber (approximately 20 addi-tional g/d in the Low-Fat Plus diet, of which approxi-mately one third was soluble), and garlic (approximately1.5 cloves/d in the Low-Fat Plus diet vs. negligibleamounts in the Low-Fat diet). The plant sterol content ofthe Low-Fat Plus diet could have contributed to our re-sults; however, it was only marginally higher than that inthe Low-Fat diet (175 mg of �-sitosterol/2000 kcal vs. 120mg of �-sitosterol/2000 kcal). The difference in LDL cho-lesterol level between participants in the 2 diet groups mayhave been attributable to a combination of 1 or more ofthese components, to other phytochemicals, or to unrecog-nized constituents.

Jenkins and colleagues (17) recently conducted a trialthat shared some characteristics of our study, including1-month feeding of hypercholesterolemic adults to lowerLDL cholesterol levels. These investigators matched energyintake, saturated fat, and cholesterol between study dietsand included more plant-based foods and specially de-signed foods in the intervention diet. In that trial, theintervention diet included more viscous fiber (providedprimarily as psyllium taken 3 times per day), plant stanolesters (provided primarily through enriched margarine),and soy protein (provided as various meat analogues). Thedifference in LDL cholesterol response to the interventiondiet versus the control diet was larger than the differencewe observed between the Low-Fat Plus and the Low-Fatdiets, which may be explained by the relatively high intakeof psyllium, plant sterols, and soy protein in the interven-tion diet designed by Jenkins and colleagues. However,another potentially important difference between the 2studies was the relatively high baseline triglyceride concen-tration in Jenkins and colleagues’ study (17) comparedwith our study (approximately 2.3 mmol/L [200 mg/dL]vs. approximately 1.5 mmol/L [130 mg/dL]). This suggeststhat Jenkins and colleagues’ participants may have had ahigher prevalence of the metabolic syndrome and thereforemay have been particularly responsive to a plant-based diet.

The design and conduct of our trial had severalstrengths. We controlled dietary intake by providing par-ticipants with all foods for all 28 days, with the exceptionof the weekly free-choice meal. In addition, we analyzedthe nutritional content of the meals using both nutritionassessment software and direct chemical analysis. Ourstudy had a high retention rate of enrolled participants(96% of those who initiated the protocol completed it),good adherence to the study diets (�1% deviation, onaverage, in both treatment groups), and successful weightmaintenance over 4 weeks in both groups.

However, our study also had limitations. We provided

95% of the food to participants, and it remains unclear towhat extent people will purchase, prepare, and consumesimilar foods on their own. Another limitation is the shortduration of the study. It is unknown whether additional ordifferent effects would have been observed over longer pe-riods.

Our results confirm that the previous version of theAHA dietary guidelines for the Step I diet (4), which fo-cused primarily on avoiding saturated fat and cholesterol, isnot as effective at lowering LDL cholesterol levels as therevised 2000 AHA dietary guidelines (2), which emphasizeincluding more plant-based foods (whole grains, vegeta-bles, legumes, and fruits) while simultaneously limiting sat-urated fat and cholesterol. These findings are consistentwith those of other studies suggesting that a plant-baseddiet benefits blood pressure and coronary heart diseaseevents (19, 33, 34). Of note, a plant-based diet is consis-tent with the dietary recommendations of the AmericanCancer Society (35).

From Stanford University Medical School and Stanford University Med-ical Center, Stanford, and Health Science Research Studies Center, LosAltos, California.

Acknowledgments: The authors gratefully acknowledge the work ofKarla J. Oliveira, MS, RD, for menu design and prestudy diet assess-ment; Pat Kolar for her work as study coordinator; and David Ahn, RD,PhD, for data programming and statistical analyses.

Grant Support: By NIH grant R01 HL57386 and by Human HealthService grant M01-RR00070, General Clinical Research Centers, Na-tional Center for Research Resources, National Institutes of Health.

Potential Financial Conflicts of Interest: None disclosed.

Requests for Single Reprints: Christopher D. Gardner, PhD, HooverPavilion, N229, 211 Quarry Road, Stanford, CA 94305-5705; e-mail,[email protected].

Current author addresses and author contributions are available at www.annals.org

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sionals from the Nutrition Committee, American Heart Association. Circulation.1996;94:1795-800. [PMID: 8840887]6. Ramsay LE, Yeo WW, Jackson PR. Dietary reduction of serum cholesterolconcentration: time to think again. BMJ. 1991;303:953-7. [PMID: 1954418]7. Anderson JW, Johnstone BM, Cook-Newell ME. Meta-analysis of the effectsof soy protein intake on serum lipids. N Engl J Med. 1995;333:276-82. [PMID:7596371]8. Crouse JR 3rd, Morgan T, Terry JG, Ellis J, Vitolins M, Burke GL. Arandomized trial comparing the effect of casein with that of soy protein contain-ing varying amounts of isoflavones on plasma concentrations of lipids and li-poproteins. Arch Intern Med. 1999;159:2070-6. [PMID: 10510993]9. Law M. Plant sterol and stanol margarines and health. BMJ. 2000;320:861-4.[PMID: 10731187]10. Kris-Etherton PM, Krummel D, Russell ME, Dreon D, Mackey S, Borch-ers J, et al. The effect of diet on plasma lipids, lipoproteins, and coronary heartdisease. J Am Diet Assoc. 1988;88:1373-400. [PMID: 2846672]11. Ripsin CM, Keenan JM, Jacobs DR Jr, Elmer PJ, Welch RR, Van Horn L,et al. Oat products and lipid lowering. A meta-analysis. JAMA. 1992;267:3317-25. [PMID: 1317928]12. Sabate J, Haddad E, Tanzman JS, Jambazian P, Rajaram S. Serum lipidresponse to the graduated enrichment of a Step I diet with almonds: a random-ized feeding trial. Am J Clin Nutr. 2003;77:1379-84. [PMID: 12791613]13. Ackermann RT, Mulrow CD, Ramirez G, Gardner CD, Morbidoni L,Lawrence VA. Garlic shows promise for improving some cardiovascular risk fac-tors. Arch Intern Med. 2001;161:813-24. [PMID: 11268223]14. Lewis B, Hammett F, Katan M, Kay RM, Merkx I, Nobels A, et al.Towards an improved lipid-lowering diet: additive effects of changes in nutrientintake. Lancet. 1981;2:1310-3. [PMID: 6118716]15. Jenkins DJ, Kendall CW, Mehling CC, Parker T, Rao AV, Agarwal S, et al.Combined effect of vegetable protein (soy) and soluble fiber added to a standardcholesterol-lowering diet. Metabolism. 1999;48:809-16. [PMID: 10381159]16. Schaefer EJ, Lichtenstein AH, Lamon-Fava S, Contois JH, Li Z, GoldinBR, et al. Effects of National Cholesterol Education Program Step 2 diets rela-tively high or relatively low in fish-derived fatty acids on plasma lipoproteins inmiddle-aged and elderly subjects. Am J Clin Nutr. 1996;63:234-41. [PMID:8561065]17. Jenkins DJ, Kendall CW, Marchie A, Faulkner DA, Wong JM, de Souza R,et al. Effects of a dietary portfolio of cholesterol-lowering foods vs lovastatin onserum lipids and C-reactive protein. JAMA. 2003;290:502-10. [PMID:12876093]18. Appel LJ, Moore TJ, Obarzanek E, Vollmer WM, Svetkey LP, Sacks FM,et al. A clinical trial of the effects of dietary patterns on blood pressure. DASHCollaborative Research Group. N Engl J Med. 1997;336:1117-24. [PMID:9099655]19. Sacks FM, Svetkey LP, Vollmer WM, Appel LJ, Bray GA, Harsha D, et al.Effects on blood pressure of reduced dietary sodium and the Dietary Approachesto Stop Hypertension (DASH) diet. DASH-Sodium Collaborative ResearchGroup. N Engl J Med. 2001;344:3-10. [PMID: 11136953]20. World Medical Association declaration of Helsinki. Recommendations guid-ing physicians in biomedical research involving human subjects. JAMA. 1997;277:925-6. [PMID: 9062334]

21. Mensink RP, Katan MB. Effect of dietary fatty acids on serum lipids andlipoproteins. A meta-analysis of 27 trials. Arterioscler Thromb. 1992;12:911-9.[PMID: 1386252]22. Gardner CD, Kraemer HC. Monounsaturated versus polyunsaturated di-etary fat and serum lipids. A meta-analysis. Arterioscler Thromb Vasc Biol. 1995;15:1917-27. [PMID: 7583572]23. Sallis JF, Haskell WL, Wood PD, Fortmann SP, Rogers T, Blair SN, et al.Physical activity assessment methodology in the Five-City Project. Am J Epide-miol. 1985;121:91-106. [PMID: 3964995]24. Allain CC, Poon LS, Chan CS, Richmond W, Fu PC. Enzymatic determi-nation of total serum cholesterol. Clin Chem. 1974;20:470-5. [PMID: 4818200]25. Sampson EJ, Demers LM, Krieg AF. Faster enzymatic procedure for serumtriglycerides. Clin Chem. 1975;21:1983-5. [PMID: 1192594]26. Warnick GR, Benderson J, Albers JJ. Dextran sulfate-Mg2� precipitationprocedure for quantitation of high-density-lipoprotein cholesterol. Clin Chem.1982;28:1379-88. [PMID: 7074948]27. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentrationof low-density lipoprotein cholesterol in plasma, without use of the preparativeultracentrifuge. Clin Chem. 1972;18:499-502. [PMID: 4337382]28. Wood PD, Stefanick ML, Dreon DM, Frey-Hewitt B, Garay SC, WilliamsPT, et al. Changes in plasma lipids and lipoproteins in overweight men duringweight loss through dieting as compared with exercise. N Engl J Med. 1988;319:1173-9. [PMID: 3173455]29. Schaefer EJ, Lamon-Fava S, Ausman LM, Ordovas JM, Clevidence BA,Judd JT, et al. Individual variability in lipoprotein cholesterol response to Na-tional Cholesterol Education Program Step 2 diets. Am J Clin Nutr. 1997;65:823-30. [PMID: 9062535]30. Katan MB, Grundy SM, Willett WC. Should a low-fat, high-carbohydratediet be recommended for everyone? Beyond low-fat diets. N Engl J Med. 1997;337:563-6. [PMID: 9262504]31. Asztalos B, Lefevre M, Wong L, Foster TA, Tulley R, Windhauser M, et al.Differential response to low-fat diet between low and normal HDL-cholesterolsubjects. J Lipid Res. 2000;41:321-8. [PMID: 10706579]32. Sprecher DL, Harris BV, Goldberg AC, Anderson EC, Bayuk LM, RussellBS, et al. Efficacy of psyllium in reducing serum cholesterol levels in hypercho-lesterolemic patients on high- or low-fat diets. Ann Intern Med. 1993;119:545-54. [PMID: 8363164]33. de Lorgeril M, Salen P, Martin JL, Monjaud I, Delaye J, Mamelle N.Mediterranean diet, traditional risk factors, and the rate of cardiovascular com-plications after myocardial infarction: final report of the Lyon Diet Heart Study.Circulation. 1999;99:779-85. [PMID: 9989963]34. Singh RB, Dubnov G, Niaz MA, Ghosh S, Singh R, Rastogi SS, et al.Effect of an Indo-Mediterranean diet on progression of coronary artery disease inhigh risk patients (Indo-Mediterranean Diet Heart Study): a randomised single-blind trial. Lancet. 2002;360:1455-61. [PMID: 12433513]35. Byers T, Nestle M, McTiernan A, Doyle C, Currie-Williams A, Gansler T,et al. American Cancer Society guidelines on nutrition and physical activity forcancer prevention: Reducing the risk of cancer with healthy food choices andphysical activity. CA Cancer J Clin. 2002;52:92-119. [PMID: 11929008]

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Current Author Addresses: Drs. Gardner, Rigby, and Farquhar and Ms.Chatterjee: Hoover Pavilion, N229, 211 Quarry Road, Stanford, CA94305-5705.Ms. Coulston: 1386 Cuernavaca Circulo, Mountain View, CA 94040-3571.Dr. Spiller: Health Research and Studies Center, 340 Second Street,Suite 7, Box 338, Los Altos, CA 94023-0338.

Author Contributions: Conception and design: C.D. Gardner, A. Coul-ston, G. Spiller, J.W. Farquhar.Analysis and interpretation of the data: C.D. Gardner, A. Coulston, A.Rigby, G. Spiller, J.W. Farquhar.Drafting of the article: C.D. Gardner, A. Coulston, A. Rigby, G. Spiller,J.W. Farquhar.Critical revision of the article for important intellectual content: C.D.Gardner, A. Coulston, A. Rigby, G. Spiller, J.W. Farquhar.Final approval of the article: C.D. Gardner, A. Coulston, A. Rigby, G.Spiller, J.W. Farquhar.Provision of study materials or patients: C.D. Gardner, L. Chatterjee.Statistical expertise: C.D. Gardner.Obtaining of funding: C.D. Gardner, J.W. Farquhar.Administrative, technical, or logistic support: A. Coulston, L. Chatterjee.Collection and assembly of data: C.D. Gardner, L. Chatterjee, A. Rigby.

Appendix Table 1. Daily Menus for the Low-Fat Plus Diet*

Food Item Amount

Menu 1Breakfast

Hot and Hearty Cereal 2 cupsSun-dried raisins 1 TWheat germ 2 TFresh blueberries 1⁄2 cupSoymilk 10 fluid ozBrewed tea 1 cup

SnackSun-dried raisins 1 oz

LunchSoy Lightburger with cheddar cheese and

tomato on whole wheat bread1

Egg 1⁄2Butter 2 tConfetti slaw 1 cupOdwalla carrot juice 8 fluid oz

SnackBlack licorice 7 piecesSeedless grapes 1⁄3 cup

DinnerWorld grains with wheat berries, brown rice,

millet1 1⁄2 cups

Garbanzo beans in tomato sauce 2 cupsEssential Salad 2 cupsLemon tahini dressing 2 TPumpkin scones 2Brewed tea 1 cup

Menu 2Breakfast

Whole wheat bread 2 slicesButter 1 1⁄4 TSmoothie 1 1⁄2 cupGrapefruit 1⁄2Brewed tea 1 cup

SnackSoy nuts 8 T

LunchGypsy soup 2 cupsParmesan cheese 3 TPilaf with dried fruit 1 cupPeanuts 1 TOdwalla Superfood juice 6 fluid oz

SnackBlack licorice 8 pieces

Dinner�Pasta Gone Wild�: rotini pasta with soy

Lightburger, vegetables2 cups

Parmesan cheese 2 1⁄2 TSpinach and mandarin salad with sesame 2 cupsEgg 3⁄4Odwalla carrot juice 8 fluid ozBrewed tea 1 cup

Menu 3Breakfast

Hot and Hearty Cereal 2 cupsMixed berries 1⁄2 cupWheat germ 2 TSoymilk 1 1⁄4 cupsBrewed tea 1 cup

SnackSun-dried raisins 1⁄8 cupBlack licorice 4 pieces

Lunch�Border Town� Burritos 1Monterey jack cheese 2 TConfetti salad 1 cupOdwalla Superfood juice 4 fluid oz

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Food Item Amount

SnackSun-dried raisins 1⁄8 cupDried almonds 2 T

DinnerExotic Stir Fry 2 cupsEgg 2⁄3Butter 5 tEssential Salad 2 cupsLemon tahini dressing 2 TOatmeal–carrot cookies 2Brewed tea 1 cup

Menu 4Breakfast

Whole wheat bread 2 slicesButter 2 tSunflower seed butter 1 1⁄2 tFresh fruit 1 cupBrewed tea 1 cup

SnackSun-dried raisins 1⁄8 cupAlmonds 1 T

LunchTeriyaki sandwich with mayonnaise on whole

wheat bread1

Alfalfa sprouts 1⁄2 cupEssential Salad 2 cupsLemon tahini dressing 2 T

SnackBlack licorice 7 pieces

DinnerGarden lasagna 2 cupsCaesar salad 3 cupsEgg 1⁄4Odwalla carrot juice 8 fluid ozBrewed tea 1 cup

Menu 5Breakfast

Hot and Hearty Cereal 2 cupsButter 2 1⁄2 tFlaxseed 1 TBlueberries 2⁄3 cupSoymilk 1 cupBrewed tea 1 cup

SnackMedium orange 1

LunchPasta fagioli soup 3 cupsEgg 3⁄4Cheddar cheese 1 ozWheat germ 3⁄4 T

DinnerTostada Grande 6 ozEssential Salad 2 cupsSunflower seeds 1 TCheddar cheese 1 ozAlfalfa sprouts 1 cupGrapes 1⁄2 cupBrewed tea 1 cup

Menu 6Breakfast

Whole wheat bread 1 sliceSunflower seed butter 1⁄2 TSmoothie 1 1⁄2 cupsPlain yogurt 1⁄2 cupBrewed tea 1 cupGrapes 1⁄4 cup

SnackSoy nuts 1⁄4 cupSun-dried raisins 1⁄2 oz

Lunch

Food Item Amount

Tempeh burger with vegetables and cheddarcheese on whole wheat bread

1

Oatmeal–carrot cookies 2Snack

Black licorice 7 piecesDinner

Parsley pesto and soba noodles 2 cupsGarlic butter 1 TSpinach and mandarin salad with sesame 2 cupsEgg 3⁄4Odwalla Superfood juice 7 fluid ozBrewed tea 1 cup

Menu 7*Breakfast

Hot and Hearty Cereal 2 cupsFlaxseed 1 TWheat germ 2 TSun-dried raisins 1 1⁄2 TSoymilk 8 fluid ozBrewed tea 1 cup

SnackBlack licorice 7 pieces

LunchGreen pepper tamale 1Cheddar cheese 1⁄2 ozEgg 1⁄4Essential Salad 2 cupsLemon tahini dressing 2 TPumpkin scones 2Butter 1 3⁄4 t

* Note: This menu was for breakfast, lunch and snacks only, no dinner.

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Appendix Table 2. Daily Menus for the Low-Fat Diet

Food Item Amount

Menu 1Breakfast

Plain bagel 1Jelly 1 TLow-fat cream cheese 3 TApple–grape juice 7 fluid ozBrewed coffee 1 cup

SnackSnackWell’s chocolate chip cookies 2

LunchTurkey bologna sandwich 1Light potato chips 1 1⁄2 ozCaffeine-free Diet Coke 12 fluid oz

SnackSnackWell’s devil’s food cookies 2

DinnerChicken–potato casserole 3 cupsApple–grape juice 7 fluid oz

Menu 2Breakfast

Frozen waffles 2Margarine 1 1⁄2 tLow-calorie syrup 1 1⁄2 TApple juice 4 fluid ozPineapple slices 3Brewed coffee 1 cup

SnackApple juice 4 fluid ozBaked Tostitos 1 oz

LunchChicken breast sandwich 1Caffeine-free Diet Coke 12 fluid oz

SnackLow-salt Goldfish crackers 1 ozApple juice 8 fluid oz

DinnerStir-fry beef with asparagus 2 cupsWonton soup 1 1⁄2 cupsBrewed coffee 1 cup

Menu 3Breakfast

Instant oatmeal 1Low-fat milk 2 1⁄2 TButter 2 1⁄2 tSoft white bread 1 1⁄2 piecesMargarine 1 1⁄2 tBrewed coffee 1 cup

SnackSnackWell’s devil’s food cookies 2

LunchTortellini salad 1 cupMedium apple 1French dinner roll 1Margarine 2 tCaffeine-free Diet Coke 12 fluid oz

SnackSnackWell’s cinnamon graham snacks 25 pieces

DinnerLean Cuisine Pizza 2Shrimp salad 1 cupCaffeine-free Diet Coke 12 fluid oz

Menu 4Breakfast

Low-fat milk 5 fluid ozBrewed coffee 1 cupMargarine 2 tEnglish muffin 1Nonfat raspberry yogurt 6 oz

Food Item Amount

SnackApple–grape juice 10 fluid ozGoldfish crackers 50 g

LunchTuna sandwich 1Medium pear 1Caffeine-free Diet Coke 12 fluid oz

SnackLemon cake pudding 1 ozApple juice 3 fluid oz

DinnerTaco salad 4 ozLow-fat milk 6 fluid ozBrewed coffee 1 cupApple–grape juice 8 fluid oz

Menu 5Breakfast

Low-fat milk 6 fluid ozRice Krispies cereal 1 3⁄4 cupsBanana 1Brewed coffee 1 cup

SnackSnackWell’s cinnamon graham snacks 20 piecesApple juice 8 fluid oz

LunchBeef burrito 1Caffeine-free Diet Coke 12 fluid oz

SnackSnackWell’s devil’s food cookies 2Apple juice 8 fluid oz

DinnerChicken–potato casserole 3 cupsCaffeine-free Diet Coke 12 fluid oz

Menu 6Breakfast

Frozen waffles 2Butter 2 3⁄4 tSyrup 2 TApple juice 5 fluid ozBrewed coffee 1 cupLow-fat milk 8 fluid oz

SnackApple–grape juice 6 fluid ozNonfat raspberry yogurt 6 oz

LunchTurkey bologna sandwich 1Light potato chips 2 ozCaffeine-free Diet Coke 12 fluid oz

SnackLemon cake pudding 1 ozLow-fat milk 8 fluid oz

DinnerGarden lasagna 3 cupsIceberg lettuce salad 1⁄2 cupFrench dinner roll 1Margarine 2 tBrewed coffee 1 cup

Menu 7*Breakfast

Rice Krispies cereal 2 cupsLow-fat milk 6 fluid ozBanana 1Brewed coffee 1 cup

SnackSnackWell’s chocolate chip cookies 2

LunchChicken breast sandwich 1Tortellini salad with cheese tortellini 1 cupFrench roll 1Margarine 3 tCaffeine-free Diet Coke 12 fluid oz

* Note: This menu was for breakfast, lunch and snacks only, no dinner.

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