Combination Between Nutrition and Exercise

Critical Review

Combination Diet and Exercise Interventions for the Treatment ofDyslipidemia: an Effective Preliminary Strategy to LowerCholesterol Levels?

Krista A. Varady and Peter J. H. Jones1

School of Dietetics and Human Nutrition, McGill University, Ste. Anne de Bellevue, QC, Canada

ABSTRACT At present, dyslipidemia is most commonly treated with drug therapy. However, because safetyconcerns regarding the use of pharmaceutical agents have arisen, a need for alternative nonpharmacologicaltherapies has become increasingly apparent. The National Cholesterol Education Program (NCEP) Adult TreatmentPanel III (ATP III) recommends lifestyle therapies, which include a combination of diet and exercise modifications,in place of drug treatment for patients who fall into an intermediate range of coronary heart disease (CHD) risk. Thisreview examined the cholesterol lowering efficacy of the following 2 NCEP-recommended combination therapies:1) low saturated fat diets combined with exercise, and 2) nutritional supplementation, i.e., fish oil, oat bran, or plantsterol supplementation, combined with exercise, in the treatment of dyslipidemia. Combination therapies areparticularly advantageous because diet and exercise elicit complementary effects on lipid profiles. More specifi-cally, diet therapies, with some exceptions, lower total (TC) and LDL cholesterol (LDL-C) concentrations, whereasexercise interventions increase HDL cholesterol (HDL-C) while decreasing triglyceride (TG) levels. With respect tospecific interventions, low saturated fat diets combined with exercise lowered TC, LDL-C, and TG concentrationsby 7–18, 7–15, and 4–18%, respectively, while increasing HDL-C levels by 5–14%. Alternatively, nutritionalsupplements combined with exercise, decreased TC, LDL-C, and TG concentrations by 8–26, 8–30, and 12–39%,respectively, while increasing HDL-C levels by 2–8%. These findings suggest that combination lifestyle therapiesare an efficacious, preliminary means of improving cholesterol levels in those diagnosed with dyslipidemia, andshould be implemented in place of drug therapy when cholesterol levels fall just above the normal range. J. Nutr.135: 1829–1835, 2005.

KEY WORDS: ● dyslipidemia ● diet ● exercise ● cholesterol ● coronary heart disease

Evidence from human clinical as well as epidemiologictrials indicate that dyslipidemia is one of the most importantmodifiable risk factors for coronary heart disease (CHD)2

(1–3). Dyslipidemia is generally characterized by increasedfasting concentrations of total cholesterol (TC), LDL choles-terol (LDL-C), and triglycerides (TG), in conjunction withdecreased concentrations of HDL cholesterol (HDL-C) (4).At present, these lipid imbalances are most routinely treatedwith pharmacological therapy. Certain commonly prescribedpharmacological agents include: 3-hydroxy-3-methylglutarylCoA reductase inhibitors (statins), bile acid sequestrants, nic-otinic acid, fibric acids, as well as the cholesterol absorptioninhibitor, ezetimibe. These cholesterol-lowering agents wereshown to decrease LDL-C levels up to 55%, increase HDL-Clevels up to 35%, and decrease TG levels as much as 50%,depending on the drug and dose (4). Although these drugsproduce desirable shifts in lipid levels within a short period of

time, several safety concerns have surfaced regarding the long-term use of these pharmacological agents (5–10). In particular,evidence suggests that the use of statins may result, althoughinfrequently, in certain forms of myopathy, i.e., mild muscleaches to severe pain, restriction in mobility, as well as grosslyelevated levels of creatine kinase (5). Additionally, liver tox-icity, characterized by increases in hepatic transaminases, wasalso shown to result from prolonged use of statins at high doses(5,7). Safety concerns regarding the use of bile acid seques-trants and fibric acids were also reported (8–10).

In view of these safety issues, the implementation of non-pharmacological therapies that beneficially modulate lipid pro-files without the risk of adverse affects would be highly advan-tageous. The Third Report of the National CholesterolEducation Program (NCEP) Adult Treatment Panel III (ATPIII) recommends lifestyle therapies in place of drug therapiesfor patients who fall into an intermediate range of CHD risk(4). The level of risk at which to implement lifestyle therapyis dependent on the individual’s fasting LDL-C concentrationas well as the number and type of CHD risk factors they possess(4). The specific dietary and lifestyle modifications outlined inthe NCEP report are termed Therapeutic Lifestyle Changes(TLC). The essential features of the ATP III TLC approachinclude: decreasing total fat intake to 25–35% of daily energy,

1 To whom correspondence should be addressed.E-mail: [email protected].

2 Abbreviations used: ATP III, Adult Treatment Panel III; CHD, coronary heartdisease; HDL-C, HDL cholesterol; LDL-C, LDL cholesterol; NCEP, National Cho-lesterol Education Program; TC, total cholesterol; TG, triglycerides; TLC, Thera-peutic Lifestyle Changes.

0022-3166/05 $8.00 © 2005 American Society for Nutritional Sciences.Manuscript received 13 February 2005. Initial review completed 20 March 2005. Revision accepted 5 May 2005.

1829

by guest on Novem

ber 19, 2013jn.nutrition.org

Dow

nloaded from

http://jn.nutrition.org/


lowering saturated fat consumption to 7% of daily energy,reducing cholesterol intake to 200 mg/d, as well as consumingcertain nutritional supplements that enhance lipid lowering(4). In accordance with these dietary guidelines, moderatephysical activity is also encouraged as an adjunctive therapy(4). Although the effect of diet and exercise therapies on lipidlevels, when applied individually, has been thoroughly re-ported (11–15), the effect of these therapies when applied incombination has yet to be summarized. Certain questions thatarise include: What effect do combination diet and exercisetherapies have on plasma lipid profiles in patients diagnosedwith dyslipidemia? How do lipid alterations resulting fromcombination lifestyle therapies compare with drug treatment?Are lifestyle therapies still relevant forms of treatment in theage of cholesterol-lowering drugs? Thus, to address these ques-tions, the goal of this review was to examine the cholesterol-lowering efficacy of the following 2 commonly prescribedcombination diet and exercise therapies: 1) low saturated fatdiets combined with exercise, and 2) nutritional supplemen-tation, i.e., fish oil, oat bran, or plant sterol supplementation,combined with exercise, in the treatment of nondiabetic,dyslipidemia.

Low saturated fat diets combined with exercise

In a clinical setting, when lifestyle modifications are pre-scribed to hypercholesterolemic patients, the most commonrecommendations include decreasing fat intake, in particular,saturated fat intake, with or without increasing daily physicalactivity. The individual effects of these 2 lifestyle therapies,low saturated fat diets and exercise, on plasma lipid profileswere carefully assessed in several recent reports (11–15). In ameta-analysis by Yu-Poth et al. (11), the effects of low satu-rated fat diets on plasma lipid levels were examined systemat-ically. From this report, it was concluded that decreases intotal and saturated fat intakes affect primarily TC and LDL-Cconcentrations, whereas they have little or no effect on HDL-C or TG levels (11). More specifically, it was shown that whendietary fat intake was limited to 30% of energy, with concur-rent saturated fat and cholesterol restrictions of �10% ofenergy and 300 mg/d, respectively, TC levels were reduced by10%, whereas LDL-C levels decreased by 12% (11). Moreover,when saturated fat and cholesterol intakes were further de-creased to �7% of energy and 200 mg/d, respectively, withtotal fat intake remaining at a constant level of 30% of energy,subjects experienced decreases of 13 and 16% in TC andLDL-C concentrations (11). In contrast to the effects of di-etary modifications on lipid levels, the most common alter-ations observed with aerobic training involved changes inHDL-C and TG concentrations (13–15). In a study by Fahl-man et al. (13), the effect of aerobic exercise on lipid levelswas examined in 45 hypercholesterolemic, elderly women.After a 10-wk intervention period, subjects assigned to theaerobic exercise intervention experienced a 20% increase inHDL-C levels, and a 14% decrease in TG concentrations (13).These changes in HDL-C and TG levels were obtained with-out any change in body weight or dietary intake (13). Changesin TC and LDL-C concentrations, as a result of endurancetraining, are observed less frequently (14). In a meta-analysisby Leon and Sanchez (14), it was reported that exercisetraining, in the absence of dietary modifications, caused meanreductions of 5% in LDL-C concentrations. These authors,however, were unable to find any sufficient effect of exercisetraining on TC levels (14). In addition, it must be noted thatthe evidence linking exercise-induced HDL-C increases to

decreased cardiovascular disease risk has yet to be firmly es-tablished.

In considering the complementary effects that low satu-rated fat diets and exercise have on cholesterol levels, wehypothesized that combining these 2 interventions would yieldhighly favorable alterations in all 4 lipid variables. Sevenstudies examined this combination therapy (Table 1) (16–22). For the most part, the diet interventions implemented inthese trials limited total fat intake to 20–30% of energy andlimited saturated fat intake to 6–10% of energy; the exerciseprograms consisted of moderate intensity training, 3–7 times/wk, for a 30- to 60-min duration. Results of these interventionson fasting lipid profiles varied. Total and LDL-C level reduc-tions ranged from 7 to 18%, and 7 to 15%, respectively(16–22). Similar reductions were noted for TG concentrations(4–18%) (16–22). The effect of the combination therapy onHDL-C levels, however, is less clear. Although some of thetrials showed significant increases ranging from 5 to 14%, amajority of the trials showed no significant effect, and someindicated that HDL-C levels may even decrease as a result oflifestyle therapy (16–22).

In view of previous findings (11–15,23–26), it can be as-sumed that the reductions in TC and LDL-C concentrationsoccurred as a result of the low saturated fat diet intervention,whereas the increases in HDL-C and decreases in TG levelsresulted from the exercise program. Nevertheless, to fullyseparate the individual contributions of each intervention onlipid levels, a parallel-arm trial that randomizes subjects into 4separate interventions groups, i.e., diet alone, exercise alone,combination of diet and exercise, and control, should beapplied. Only 1 of the studies (20) reviewed in this reportemployed this design. In this study by Stefanick et al. (20),those participating in the diet intervention consumed a diet inwhich total fat and saturated fat was limited to 30 and 7% ofenergy, respectively, and those participating in the exerciseintervention trained 3 times/wk for 60 min, under supervisedconditions. When this design was applied, it was noted thatthe diet group experienced the greatest reductions in TC andLDL cholesterol levels (7.9 and 7.3%, respectively), the exer-cise group experienced significant increases in HDL-C anddecreases in TG levels (2.3 and 12.2%, respectively), whereasthe combination group had favorable shifts in all 4 lipidvariables (20). In accordance with previous findings, the re-sults of this study indicate that, when combined, low saturatedfat diets and exercise have complementary effects on lipidlevels, in turn producing a more optimal lipid profile than eachintervention alone.

The large variability between studies in treatment-inducedlipid lowering may be due in part to the different trial dura-tions. When the trials were ordered according to study length,it became apparent that the studies that achieved the greatestlipid altering effects were long-term trials (16–22). For in-stance, in a study conducted by Niebauer et al. (22), men withdiagnosed coronary artery disease experienced declines of 18and 7% in TC and LDL-C, respectively, and an increase of14% in HDL-C concentrations after a 6-y combination dietand exercise program. Similarly, in a trial performed by Ste-fanick et al. (20), after 52 wk of treatment, TC and LDL-Cconcentrations decreased by 18 and 15%, respectively. Incomparison, studies with slightly shorter trial periods have alsodemonstrated favorable lipid modifications (16,17,19). For in-stance, when Andersen et al. (17) applied a combinationtherapy for 16 wk, significant reductions in TC and LDL-Clevels of 11 and 10%, respectively, were noted. Thus, thesefindings suggest that LDL lowering resulting from these life-style interventions may be achieved after 16 wk of treatment;

VARADY AND JONES1830

by guest on Novem


Dow

nloaded from



however, for maximal LDL lowering to occur, the interventionshould be applied for 1 y. These results also imply that, asdemonstrated by the 6-y follow-up study, the degree of lipidlowering reached after 1 y of therapy may be maintained if thelifestyle intervention is continued.

The different diet interventions applied may also accountfor the discrepancies in cholesterol lowering noted betweentrials. The diet therapies implemented varied considerably intheir percentage of allowances for total fat and saturated fat(16–22). Nevertheless, no clear positive or negative associa-tions could be established for the effect of percentage of fat,i.e., total fat or saturated fat, on individual lipid variables.Although it is not evident from the present findings, it ispostulated that very low fat diets, i.e., diets with �20% energyfrom fat, would potentially adversely affect lipid profiles (27–30). This could potentially occur as a result of an increasedpercentage of carbohydrate in the diet to compensate for thelack of fat. As demonstrated by several recent studies (27–30),increases in carbohydrate intake could potentially raise TGlevels in the blood, resulting in less favorable lipid profiles.

This relation, however, was not noted in any of the combina-tion diet and exercise trials currently under review.

The weight loss noted in 6 of the 7 studies reviewed(16–21), could also potentially account for the lipid-loweringinconsistencies observed among trials. The weight reductionobserved in these studies, expressed as a post-treatment per-centage of change from initial body mass, ranged from 2 to10% (16–21). Although no clear dose-response relation be-tween weight loss and lipid modulations could be determined,it would appear that those trials that experienced a weightreduction �5% of initial body weight, observed the mostsignificant changes in TC and LDL-C concentrations. Forinstance, in the study by Andersen et al. (17), in which thesubjects experienced a 10% decrease in body mass, TC andLDL-C levels decreased by 10.9 and 10.7%, respectively. Sim-ilarly, in the study by Williams et al. (21), in which body massdecreased by 7% over the course of the 52-wk trial, LDL-Clevels decreased by 15.2%. In contrast, no clear associationsbetween weight loss and HDL-C or TG modulations could bedetermined. In examining separately the study by Niebauer et

TABLE 1

Randomized clinical trials examining the effect of low saturated fat diets combined with exercise on lipid profiles

Reference Subjects1 Design2 Diet interventionExercise

intervention

Post-treatmentbody weight

(% change)3,4

Post-treatment blood lipidconcentrations (% change)3,4

TC LDL-C HDL-C TG

(16) n � 44OB, HCM/F

9 wk1. Diet � exercise2. Control

2090–4190 kJ/d deficit27% total fat6% saturated fat

Endurance trainingSupervised30–45 min, 3�/wk

�5.2* �8.6* �6.7* �14.6* 2.4

(17) n � 38OB, HCF

16 wk1. Diet � aerobics2. Diet � moderate activity

5020 kJ/d�30% total fat�10% saturated fat

1. AerobicsSupervised45 min, 3�/wk

�9.6* �10.9* �10.7* �9.4* �17.9*

2. WalkingUnsupervised30 min/d

�8.8* �9.3* �6.3* �10.3* �14.6*

(18) n � 32HCM/F

24 wk2 CETP genotype groups:1. CETP B1B1

No kJ/d limit�30% total fat�10% saturated fat

Endurance trainingSupervised40 min, 3�/wk

�0.9 �1.0 �2.1 4.7* �10.4

2. CETP B1B2 �1.5* 2.9 3.0 13.2* �13.8

(19) n � 535NCF

24 wk1. Diet � exercise2. Control

5440–6280 kJ/d�25% total fat�7% saturated fat

WalkingUnsupervised30–60 min/d

�4.8* �6.7* �9.5* �3.4* �4.3*

(20) n � 377OB, HCM/F

52 wk1. Diet � exercise2. Exercise3. Diet4. Control

No kJ/d limit�30% total fat�7% saturated fat


�4.5* �17.5* �14.5* �1.1 �10.3

(21) n � 116OBM

52 wk1. Diet � exercise2. Diet

2090 kJ/d deficit�30% total fat�10% saturated fat

RunningUnsupervisedFrequency notspecified

�6.6* — �15.2 16.5* —

(22) n � 113 6 y No kJ/d limit Endurance training 0.0 �17.6* �6.9 14.0* �17.5*CAD, HCM

1. Diet � exercise(supervised)2. Diet � exercise (non-supervised)

�20% total fatPolyunsaturated:saturated fat ratio � 1

30–60 min/d 5.0 �4.3 1.0 12.1* �17.7

1 OB, obese; HC, hypercholesterolemic [TC � 200 mg/dL (5.17 mmol/L), LDL-C � 100 mg/dL (2.56 mmol/L), HDL-C in normal range 40–60 mg/dL(1.04–1.55 mmol/L)]; NC, normocholesterolemic [TC � 199 mg/dL (5.15 mmol/L) and LDL-C � 99 mg/dL (2.55 mmol/L), HDL-C in normal range40–60 mg/dL (1.04–1.55 mmol/L)]; CAD, coronary artery disease patients; M, male; F, female.

2 Randomized parallel-arm trials: 1, Intervention group 1; 2, Intervention group 2; 3, Intervention group 3; 4, Intervention group 4.3 Post-treatment percentage of change relative to baseline, results for combination diet � exercise intervention groups.4 * Significant changes in the combination diet � exercise intervention groups, P � 0.05, as reported for each study.

DIET AND EXERCISE THERAPY FOR DYSLIPIDEMIA 1831

by guest on Novem


Dow

nloaded from



al. (22), in which significant weight loss was not observed,interesting relations among study design, lack of weight loss,and lipid alterations were noted. In this study, subjects wererandomized either to a supervised combination diet and exer-cise group, or a nonsupervised combination diet and exercisegroup for a 6-y trial period. Throughout the study, the subjectsexercised every day for 30–60 min, and consumed a dietconsisting of �20% of energy as total fat. Surprisingly, al-though the supervised combination group did not experienceany significant weight reduction, this group witnessed signifi-cant reductions in TC, LDL-C, and TG concentrations of17.6, 6.9, and 17.5%, respectively, whereas HDL-C levelsincreased by 14.0%. In comparison, in the nonsupervisedcombination group, which experienced a nonsignificant bodymass reduction of 5%, TC concentrations decreased by 4%,LDL-C levels increased by 1%, and HDL-C and TG levelswere modulated to an extent similar to that in the supervisedgroup. The unclear association between diet/exercise-inducedweight loss and lipid lowering observed in this review was alsosummarized in other recent reports (14). Although it has beenshown consistently that decreases in body weight beneficiallymodulate cholesterol profiles (31–34), a clear dose-responserelation between decreased body mass and degree of choles-terol lowering has yet to be established (14). Establishing thisdose-response relation has been difficult because isolating the

effect of body weight reduction vs. treatment effect on lipidprofiles is practically impossible. Accordingly, as an attempt toisolate the effect of this confounder, a trial should be con-ducted that examines the effect of a combination diet andexercise therapy on lipid levels, with and without energyrestriction. Only if such a study were performed, might theindependent effects of treatment vs. treatment-induced weightloss on lipid concentrations be determined.

Nutritional supplementation combined with exercise

Some hypercholesterolemic patients may find it difficult toadhere to a tightly regimented low saturated fat diet; thus,compliance with the lipid-lowering therapy may be compen-sated (35,36). For these patients, supplementing the diet withcertain functional foods or nutraceuticals known to enhancelipid lowering, i.e., fish oil, oat bran, or plant sterols, may be amore appropriate strategy (37). Randomized clinical trials ex-amining lifestyle therapies that combine nutritional supple-mentation with exercise training are listed in Table 2 (38–42).

Fish oil supplementation combined with exercise. Fish oilsupplementation has gained considerable attention in recentyears because it was shown to beneficially modulate lipidprofiles in a way that confers protection against future CHD

TABLE 2

Randomized clinical trials examining the effect of nutritional supplements combined with exercise on lipid profiles

Reference Subjects1 Design2 Diet interventionExercise

intervention

Post-treatmentbody weight

(% change)3,4

Post-treatment blood lipidconcentrations (% change)3,4

TC LDL-C HDL-C TG

Fish oil(38) n � 53 4 wk 5024 kJ/d Swimming �3.9* �12.2* �16.0* 8.3* �20.3*

CAD, HCM

1. Diet � exercise � fish oil2. Diet � exercise � rapeseed

oil

�30% total fat1. 12 g/d fish oil2. 12 g/d rapeseed

Supervised20 min, 6�/wk

�3.9* �14.4* �20.3* 0.9 �5.1

(39) n � 34HCM/F

12 wk1. Exercise � fish oil2. Fish oil3. Corn oil4. Control

No kJ/d limitNormal diet45 g/d fish oil

Endurance trainingUnsupervised30–60 min, 3�/wk

— �9.8* �8.0* 2.0* �38.9*

Oat bran(40) n � 13

HCM/F

4 wk1. Diet � exercise � oat branNo control group

No kJ/d limit�30% total fat100 g oat bran(�-glucan dose notspecified)

Walking, running,swimmingUnsupervised40–60 min/d

�0.4 �8.2 �9.9 0.8 �12.1

(41) n � 235OB, HCM

4 wk1. Diet � exercise � oat bran2. Diet � exercise3. Control

4190 kJ/d deficit�30% total fat35–50 g oat bran(�-glucan dose notspecified)

Endurance trainingSupervised60 min/d

— �26.0* �30.3* �4.8 �38.7

Plant sterols(42) n � 73

HCM/F

8 wk1. Exercise � plant sterols2. Plant sterols3. Exercise4. Control

No kJ/d limitNormal diet1.8 g/d plantsterols


�1.1* �7.7* �8.3 7.5* �11.8*

1 OB, obese; HC, hypercholesterolemic [total cholesterol � 200 mg/dL (5.17 mmol/L), LDL-cholesterol � 100 mg/dL (2.56 mmol/L), HDL-cholesterol in normal range 40–60 mg/dL (1.04–1.55 mmol/L)]; CAD, coronary artery disease patients; M, male; F, female.

2 Randomized parallel-arm trials: 1, Intervention group 1; 2, Intervention group 2; 3, Intervention group 3; 4, Intervention group 4.3 Post-treatment percent change relative to baseline, results for combination diet � exercise intervention groups.4 * Significant changes in the combination diet � exercise intervention groups, P � 0.05, as reported for each study.


by guest on Novem


Dow

nloaded from



(43). Although the majority of clinical data support the no-tion of fish oil as a cardioprotective agent, epidemiologicevidence that has clouded this issue has surfaced recently (44).These conflicting findings should be kept in mind while re-viewing the evidence from clinical trials. This being said, in arecent systematic review by Lewis et al. (45), it was reportedthat supplementation with fish oil decreased TC and TGconcentrations by 12 and 29%, respectively, while increasingHDL-C levels by 10%. The studies examined in the review(45) employed supplements containing mixtures of eicosapen-taenoic acid and docosahexaenoic acid in the range of 1–5 g/d.Although most reports indicate favorable effects on the above-mentioned lipid variables, the effects of fish oil on LDL-C aremore controversial (46–49). Although some clinical trialsindicated that fish oil has no effect on LDL-C concentrations(46,47), others showed that fish oil causes these concentra-tions to increase (48,49). Although the precise reason forthese equivocal findings has yet to be determined, it wassuggested that apolipoprotein E phenotypes may play a role insubject response to fish oil therapy (50,51). In particular,increases in LDL-C levels after fish oil supplementation wereobserved in subjects possessing the �4 allele, whereas no ad-verse shifts were noted in those possessing the �3 allele(50,51). Thus, in future clinical practice, it may be necessaryto screen for such diet-gene interactions before certain nutri-tional therapies, such as fish oil, may be recommended toindividuals diagnosed with dyslipidemia.

The potential synergistic or additive effect of fish oil sup-plementation when combined with exercise on lipid levels wasexamined in only 2 randomized control trials (38,39). In astudy conducted by Hermann et al. (38), 12 g/d of fish oilsupplementation in conjunction with swimming 6 times/wkfor a period of 4 wk lowered TC and LDL-C concentrations by12 and 16%, respectively. In addition, HDL-C levels increasedby 8%, whereas TG concentrations decreased by 20% (38).Similar results were noted in a study by Warner et al. (39),which tested the effect of fish oil (45 g/d) alone or in combi-nation with exercise, on lipid profiles. After a 12-wk interven-tion period, LDL-C levels were significantly decreased in thecombination group, whereas HDL-C concentrations increasedin both the fish oil and combination group (39). Thus, al-though there are only a few studies from which to drawconclusions, these results suggest that when combined, fish oiland exercise may help to lower the risk of CHD by favorablymodulating all 4 lipid variables. In particular, combining these2 interventions results in a beneficial, additive effect on TGconcentrations, while in some way producing a positive, syn-ergistic effect on LDL-C concentrations. The reason for thesesignificant reductions in LDL-C levels, however, remains un-clear. Because neither fish oil supplementation nor exercisetherapy was shown to positively modulate LDL-C concentra-tions when applied alone, it is unusual that the combinatoryeffect of these 2 treatments would synergistically produce suchfavorable alterations. Nevertheless, on the basis of the presentfindings, combining fish oil supplementation with a regularexercise program could be recommended in clinical practice asan effective strategy to beneficially alter lipid profiles in thoseat risk for CHD. Future research should aim to examine themechanisms of action underlying the synergistic relationshipof this combination therapy on lipid levels, and in addition,the role that diet-gene interactions may play in modulatingthis effect.

Oat bran supplementation combined with exercise. Evi-dence suggests that viscous, soluble fibers, such as oat bran,may have a substantial hypocholesterolemic effect (52–54). Inparticular, supplementing the diet with oat products was

shown to produce significant reductions in both TC and LDL-C concentrations, while having little effect on either HDL-Cor TG levels (52–54). In a study that supplemented mildlyhypercholesterolemic men and women for 5 wk with 50–75 goat fiber extract/d, LDL-C concentrations were shown to de-crease by 21% (55). Recent evidence indicates that the lipid-lowering effect of oat products may be attributed to their mainsoluble fiber component, �-glucan (56). To elucidate thespecific mechanism of action, it was suggested that �-glucandecreases the absorption of ingested nutrients and bile acids byincreasing the viscosity of intestinal contents (56). The pre-cise dose of �-glucan required to elicit such lipid-loweringeffects, however, remains unclear (56). In a study by Davidsonet al. (57), it was shown that supplementing the diet with 3.6,4.0, and 6.0 g of �-glucan from oatmeal resulted in LDL-Cconcentration reductions of 10, 16, and 12%, respectively. Assuch, this study was not able to establish a dose-responserelation because the highest dose of �-glucan produced anintermediate hypocholesterolemic response (57). Althoughsolid conclusions regarding �-glucan dose have yet to be made,it would appear that a minimal dose of 3 g/d is required toproduce clinically relevant reductions in both TC and LDL-Cconcentrations (56).

In studies that have combined oat bran supplementationwith exercise, consistent and substantial plasma lipid decreaseswere demonstrated (40,41). After 4 wk of supplementing with35–50 g oat bran/d combined with supervised endurance train-ing for 60 min/d, Berg et al. (41) demonstrated reductions inTC and LDL-C of 26 and 30%, respectively. Similarly, in a4-wk study by Kelley et al. (40), which combined 100 g/d ofoat bran supplementation with nonsupervised training for40–60 min/d, TC and LDL-C concentrations decreased by 8and 9%, respectively. HDL-C and TG concentrations, how-ever, were not significantly affected in either study (40,41).The lack of effect on HDL-C levels could potentially be due tothe short-term duration of the study. Recent evidence suggeststhat regular exercise must be performed for a minimum periodof 8 wk to promote HDL-C elevations (14). In view of this,future studies should be conducted that implement this com-bination therapy for longer trial durations, to determinewhether further LDL-C reductions, as well as potential HDL-C–raising effects occur. The large discrepancy in TC andLDL-C lowering seen between the 2 studies is most likely dueto the different diet and exercise regimens prescribed. In thestudy by Berg et al. (41), a diet that had a 4190 kJ/d deficit, wasimplemented in combination with a supervised daily exerciseprogram. In contrast, in the study by Kelley et al. (40), neitherenergy intake nor exercise compliance was controlled. Thus,in considering the dietary energy deficit as well as the tightlycontrolled training protocol imposed in the study by Berg et al.(41), it is not surprising that these subjects experienced muchgreater lipid reductions than those participating in the studyby Kelley et al. (40). Interestingly, neither study reported thedose of �-glucan contained in the quantity of oat bran pre-scribed. Because levels of �-glucan vary among different oatproducts (56), it is not possible to approximate the daily doseof �-glucan implemented in these supplementation regimens.However, because significant reductions were noted in bothTC and LDL-C levels, it can be assumed that the minimaldose of 3 g/d of �-glucan was consumed. Thus, from thepresent findings, combining oat bran supplementation, con-taining a minimal dose of 3 g �-glucan/d, with daily exercisewould appear to be an effective natural therapy to decreaseboth TC and LDL-C levels in hypercholesterolemic individ-uals.


by guest on Novem


Dow

nloaded from



Plant sterols combined with exercise. Plant sterols, plantcompounds that are structurally similar to cholesterol, wereshown to lower lipid levels in humans by inhibiting cholesterolabsorption from the intestine (58–60). Food sources of plantsterols include vegetable oils, seeds, and nuts (60). Increasingthe dietary intake of these compounds is also possible throughthe consumption of certain products that have been supple-mented with plant sterols, such as margarines, yogurts, cerealbars, and fruit juices (58). In a meta-analysis of 21 trials ofplant sterol supplementation (58), it was shown that a near-maximum effect of a 10% reduction in LDL-C occurs at a doseof 2 g/d. Total cholesterol levels were shown to be reduced toa similar extent (58). Although plant sterols consistentlylower TC and LDL-C concentrations, evidence suggests thatthese nutritional supplements have no effect on HDL-C or TGlevels (58–60). Thus, to achieve the most advantageous lipidalterations, combining this supplement with a therapy thatbeneficially modulates both HDL-C and TG levels, such asexercise, would be highly favorable. Only 1 trial (42) to datetested the effects of this combination strategy on cholesterolconcentrations. After an 8-wk trial period in which the indi-vidual vs. combined effects of plant sterols and exercise werecompared, it was shown that the combination group experi-enced the most beneficial alterations in lipid profiles becauseeach lipid variable was shifted in a favorable direction (42).More specifically, TC, LDL-C, and TG levels decreased by 7.7,8.3, and 11.8%, respectively, whereas HDL-C concentrationsincreased by 7.5% (42). These favorable alterations wereachieved by consuming 1.8 g/d of plant sterols, while perform-ing endurance training 3 times/wk for a period of 25–40 min(42). In considering the degree to which this combinationtherapy was able to favorably alter all 4 lipid variables withouthaving to change dietary patterns, this lifestyle strategy couldbe considered a practical method for lowering cholesterollevels in hypercholesterolemic patients.

In summary, it is clear that lifestyle therapies that combinediet and exercise interventions are efficacious, nonpharmaco-logical strategies for the treatment of dyslipidemia. Combina-tion lifestyle treatments are particularly advantageous becausediet and exercise elicit complementary effects on lipid profiles.More specifically, diet therapies, with some exceptions, actprimarily to lower TC and LDL-C concentrations, and exer-cise interventions increase HDL-C while decreasing TG lev-els. Thus, when combined, favorable shifts in all 4 lipid vari-ables are demonstrated. In this review, 2 combination lifestyletherapies outlined in the ATP III TLC guidelines, i.e., lowsaturated fat diets combined with exercise as well as nutri-tional supplements combined with exercise, were examined.Results revealed that therapies involving low saturated fatdiets combined with exercise lowered TC, LDL-C, and TGconcentrations by 7–18, 7–15, and 4–18%, respectively, whileincreasing HDL-C levels by 5–14%. When nutritional supple-ments, i.e., fish oil, oat bran, and plant sterols, were combinedwith exercise, these combination lifestyle therapies decreasedTC, LDL-C, and TG concentrations by 8–26, 8–30, and12–39%, respectively, while increasing HDL-C concentrations2–8%. Additionally, it was also noted that in trials in whichthe combination intervention induced weight loss �5% ofinitial body weight, TC and LDL-C concentrations were de-creased more than in those trials that did not experience thisdegree of weight loss. In contrast, no clear associations be-tween treatment-induced weight loss and HDL-C or TG levelmodulations could be determined.

Thus, in considering the degree to which cholesterol levelswere favorably altered, it is evident that these nonpharmaco-logical interventions remain valuable strategies in the treat-

ment of dyslipidemia. In particular, these lifestyle therapies arean efficacious means of lowering cholesterol levels in thoseindividuals whose LDL-C levels fall just above the normalrange. For these individuals, who require only a 5–25% de-crease in LDL-C concentrations, combination interventionsthat elicit this degree of cholesterol lowering should be imple-mented as a preliminary measure. Furthermore, implementinglifestyle therapies as a first line of treatment is particularlyimportant in view of drug-induced adverse events that areoccasionally observed with pharmacological treatment. Addi-tionally, applying combination lifestyle interventions as anadjunctive therapy to drug treatment may help to decrease thedose of the lipid-lowering drug required to meet treatmentgoals. Moreover, combination lifestyle therapies are cost effec-tive, and may further benefit the overall health of the indi-vidual, whether they are hypercholesterolemic or within thenormal range, by supporting weight control, lowering bloodpressure, and improving glucose tolerance. In conclusion,combination lifestyle therapies are an efficacious means ofimproving cholesterol levels in those diagnosed with dyslipi-demia, and should be implemented over and above drug ther-apy when cholesterol levels fall just above the normal range.

LITERATURE CITED

1. Ferdinand, K. C. (2004) The importance of aggressive lipid manage-ment in patients at risk: evidence from recent clinical trials. Clin. Cardiol. 27:12–15.

2. Meagher, E. A. (2004) Addressing cardiovascular disease in women:focus on dyslipidemia. J. Am. Board Fam. Pract. 17: 424–437.

3. Watkins, L. O. (2004) Epidemiology and burden of cardiovasculardisease. Clin. Cardiol. 27: 2–6.

4. National Cholesterol Education Program (2001) Third Report of theExpert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol inAdults. NIH Publication no. 01–3670. National Institutes of Health, Bethesda, MD.

5. Bellosta, S., Paoletti, R. & Corsini, A. (2004) Safety of statins: focus onclinical pharmacokinetics and drug interactions. Circulation 109: 50–57.

6. Taylor, A. J., Grace, K., Swiecki, J., Hyatt, R., Gibbs, H., Sheikh, M.,O’Malley, P. G, Lowenthal, S. P., West, M., Spain, J., Maneval, K. & Jones, D. L.(2001) Lipid-lowering efficacy, safety, and costs of a large-scale therapeuticstatin formulary conversion program. Pharmacotherapy 21: 1130–1139.

7. de Denus, S., Spinler, S. A., Miller, K. & Peterson, A. M. (2004) Statinsand liver toxicity: a meta-analysis. Pharmacotherapy 24: 584–591.

8. Lozada, A. & Dujovne, C. A. (1994) Drug interactions with fibric acids.Pharmacol. Ther. 63: 163–176.

9. Blane, G. F. (1987) Comparative toxicity and safety profile of fenofi-brate and other fibric acid derivatives. Am. J. Med. 27: 26–36.

10. Kajinami, K. & Takekoshi, N. (2002) Cholesterol absorption inhibitorsin development as potential therapeutics. Expert Opin. Investig. Drugs. 11: 831–835.

11. Yu-Poth, S., Zhao, G., Etherton, T., Naglak, M., Jonnalagadda, S. &Kris-Etherton, P. M. (1999) Effects of the National Cholesterol EducationProgram’s Step I and Step II dietary intervention programs on cardiovasculardisease risk factors: a meta-analysis. Am. J. Clin. Nutr. 69: 632–646.

12. Kris-Etherton, P. M., Binkoski, A. E., Zhao, G., Coval, S. M., Clemmer,K. F., Hecker, K. D., Jacques, H. & Etherton T. D. (2002) Dietary fat: assessingthe evidence in support of a moderate-fat diet; the benchmark based on lipopro-tein metabolism. Proc. Nutr. Soc. 61: 287–298.

13. Fahlman, M. M., Boardley, D., Lambert, C. P. & Flynn, M. G. (2002)Effects of endurance training and resistance training on plasma lipoprotein pro-files in elderly women. J. Gerontol. A. Biol. Sci. Med. Sci. 57: 54–60.

14. Leon, A. S. & Sanchez, O. A. (2001) Response of blood lipids toexercise training alone or combined with dietary intervention. Med. Sci. SportsExerc. 33: 502–515.

15. Durstine, J. L., Grandjean, P. W., Davis, P. G., Ferguson, M. A., Alderson,N. L. & DuBose, K. D. (2001) Blood lipid and lipoprotein adaptations toexercise: a quantitative analysis. Sports Med. 31: 1033–1062.

16. Miller, E. R., Erlinger, T. P., Young, D. R., Jehn, M., Charleston, J.,Rhodes, D., Wasan, S. K. & Appel, L. J. (2002) Results of the Diet, Exercise,and Weight Loss Intervention Trial (DEW-IT). Hypertension 40: 612–618.

17. Andersen, R. E., Wadden, T. A., Bartlett, S. J., Zemel, B., Verde T. J. &Franckowiak, S. C. (1999) Effects of lifestyle activity vs structured aerobicexercise in obese women: a randomized trial. J. Am. Med. Assoc. 281: 335–340.

18. Wilund, K. R., Ferrell, R. E., Phares, D. A., Goldberg, A. P. & Hagberg,J. M. (2002) Changes in high-density lipoprotein-C subfractions with exercisetraining may be dependent on cholesteryl ester transfer protein (CETP) genotype.Metabolism 51: 774–778.

19. Simkin-Silverman, L., Wing, R. R., Hansen, D. H., Klem, M. L., Pasagian-Macaulay, A. P., Meilahn, E. N. & Kuller, L. H. (1995) Prevention of cardiovas-


by guest on Novem


Dow

nloaded from



cular risk factor elevations in healthy premenopausal women. Prev. Med. 24:509–517.

20. Stefanick, M. L., Mackey, S., Sheehan, M., Ellsworth, N, Haskell, W. L. &Wood, P. D. (1998) Effects of diet and exercise in men and postmenopausalwomen with low levels of HDL cholesterol and high levels of LDL cholesterol.N. Engl. J. Med. 339: 12–20.

21. Williams, P. T., Krauss, R. M., Stefanick, M. L., Vranizan, K. M. & Wood,P. D. (1994) Effects of low-fat diet, calorie restriction, and running on lipopro-tein subfraction concentrations in moderately overweight men. Metabolism 43:655–663.

22. Niebauer, J., Hambrecht, R., Velich, T., Hauer, K., Marburger, C., Kal-berer, B., Weiss, C., von Hodenberg, E., Schlierf, G., Schuler, G., Zimmermann, R.& Kubler, W. (1997) Attenuated progression of coronary artery disease after 6years of multifactorial risk intervention: role of physical exercise. Circulation 96:2534–2541.

23. Sharman, M. J., Gomez, A. L., Kraemer, W. J. & Volek, J. S. (2004)Very low-carbohydrate and low-fat diets affect fasting lipids and postprandiallipemia differently in overweight men. J. Nutr. 134: 880–885.

24. Beauchesne-Rondeau, E., Gascon, A., Bergeron, J. & Jacques, H.(2003) Plasma lipids and lipoproteins in hypercholesterolemic men fed a lipid-lowering diet containing lean beef, lean fish, or poultry. Am. J. Clin. Nutr. 77:587–593.

25. Leon, A. S., Gaskill, S. E., Rice, T., Bergeron, J., Gagnon, J., Rao, D. C.,Skinner, J. S., Wilmore, J. H. & Bouchard, C. (2002) Variability in the responseof HDL cholesterol to exercise training in the HERITAGE Family Study. Int.J. Sports Med. 23: 1–9.

26. Lavie, C. J. & Milani, R. V. (1996) Effects of cardiac rehabilitation andexercise training programs in patients � or � 75 years of age. Am. J. Cardiol. 78:675–677.

27. McCarty, M. F. (2004) An elevation of triglycerides reflecting de-creased triglyceride clearance may not be pathogenic—relevance to high-carbo-hydrate diets. Med. Hypotheses 63: 1065–1073.

28. Abeywardena, M. Y. (2003) Dietary fats, carbohydrates and vasculardisease: Sri Lankan perspectives. Atherosclerosis 171: 157–161.

29. Archer, W. R., Lamarche, B., Deriaz, O., Landry, N., Corneau, L., Despres,J. P., Bergeron, J., Couture, P. & Bergeron, N. (2003) Variations in bodycomposition and plasma lipids in response to a high-carbohydrate diet. Obes.Res. 11: 978–986.

30. Mamo, J. C., James, A. P., Soares, M. J., Purcell, K., Griffiths, D. &Schwenke, J. L. (2004) Carbohydrate rich diets exacerbate postprandial lipae-mia in moderately dyslipidemic subjects, whereas red meat protein-enricheddiets have no adverse effects. Asia Pac. J. Clin. Nutr. 13: 52–54.

31. Orzano, A. J. & Scott, J. G. (2004) Diagnosis and treatment of obesityin adults: an applied evidence-based review. J. Am. Board Fam. Pract. 17:359–369.

32. Avenell, A., Broom, J., Brown, T. J., Poobalan, A., Aucott, L., Stearns,S. C., Smith, W. C., Jung, R. T., Campbell, M. K. & Grant, A. M. (2004)Systematic review of the long-term effects and economic consequences oftreatments for obesity and implications for health improvement. Health Technol.Assess. 8: 1–182.

33. Sowers, J. R. (2003) Obesity as a cardiovascular risk factor. Am. J.Med. 115: 37–41.

34. Schaefer, E. J., Lichtenstein, A. H., Lamon-Fava, S., McNamara, J. R.,Schaefer, M. M., Rasmussen, H. & Ordovas, J. M. (1995) Body weight andlow-density lipoprotein cholesterol changes after consumption of a low-fat adlibitum diet. J. Am. Med. Assoc. 274: 1450–1455.

35. Davidson, M. H. (2002) Strategies to improve Adult Treatment Panel IIIguideline adherence and patient compliance. Am. J. Cardiol. 89: 8–20.

36. Van Horn, L. & Kavey, R. E. (1997) Diet and cardiovascular diseaseprevention: what works? Ann. Behav. Med. 19: 197–212.

37. Sherman, A. M., Bowen, D. J., Vitolins, M., Perri, M. G., Rosal, M. C.,Sevick, M. A. & Ockene, J. K. (2000) Dietary adherence: characteristics andinterventions. Control. Clin. Trials 21: 206–211.

38. Herrmann, W., Biermann, J. & Kostner, G. M. (1995) Comparison ofeffects of N-3 to N-6 fatty acids on serum level of lipoprotein(a) in patients withcoronary artery disease. Am. J. Cardiol. 76: 459–462.

39. Warner, J. G., Ullrich, I. H., Albrink, M. J. & Yeater, R. A. (1989) Com-bined effects of aerobic exercise and omega-3 fatty acids in hyperlipidemicpersons. Med. Sci. Sports Exerc. 21: 498–505.

40. Kelley, M. J., Hoover-Plow, J, Nichols-Bernhard, J. F., Verity, L. S. &Brewer, H. (1994) Oat bran lowers total and low-density lipoprotein cholesterol

but not lipoprotein(a) in exercising adults with borderline hypercholesterolemia.J. Am. Diet. Assoc. 94: 1419–1421.

41. Berg, A., Konig, D., Deibert, P., Grathwohl, D., Berg, A., Baumstark,M. W., Franz & I. W. (2003) Effect of an oat bran enriched diet on theatherogenic lipid profile in patients with an increased coronary heart disease risk.A controlled randomized lifestyle intervention study. Ann. Nutr. Metab. 47:306–311.

42. Varady, K. A., Ebine, N., Vanstone, C. A., Parsons, W. E., Jones, P. J.(2004) Plant sterols and endurance training combine to favorably alter plasmalipid profiles in previously sedentary hypercholesterolemic adults after 8 wk.Am. J. Clin. Nutr. 80: 1159–1166.

43. Wijendran, V. & Hayes, K. C. (2004) Dietary n-6 and n-3 fatty acidbalance and cardiovascular health. Annu. Rev. Nutr. 24: 597–615.

44. Hooper, L., Thompson, R. L., Harrison, R. A., Summerbell, C. D., Moore,H., Worthington, H. V., Durrington, P. N., Ness, A. R., Capps, N. E., Davey-Smith,G., Riemersma, R. A. & Ebrahim, S. B. (2004) Omega 3 fatty acids forprevention and treatment of cardiovascular disease. Cochrane Database Syst.Rev. 4: CD003177.

45. Lewis, A., Lookinland, S., Beckstrand, R. L. & Tiedeman, M. E. (2004)Treatment of hypertriglyceridemia with omega-3 fatty acids: a systematic review.J. Am. Acad. Nurse Pract. 16: 384–395.

46. Nestel, P., Shige, H., Pomeroy, S., Cehun, M., Abbey, M. & Raederstorff,D. (2002) The n-3 fatty acids eicosapentaenoic acid and docosahexaenoicacid increase systemic arterial compliance in humans. Am. J. Clin. Nutr. 76:326–330.

47. Grimsgaard, S., Bonaa, K. H., Hansen, J. B. & Nordoy, A. (1997) Highlypurified eicosapentaenoic acid and docosahexaenoic acid in humans have similartriacylglycerol-lowering effects but divergent effects on serum fatty acids. Am. J.Clin. Nutr. 66: 649–659.

48. Mori, T. A., Burke, V. & Puddey, I. B. (2000) Purified eicosapentaenoicand docosahexaenoic acids have differential effects on serum lipids and lipopro-teins, LDL particle size, glucose, and insulin in mildly hyperlipidemic men. Am. J.Clin. Nutr. 71: 1085–1094.

49. Davidson, M. H., Maki, K. C., Kalkowski, J., Schaefer, E. J., Torri, S. A. &Drennan, K. B. (1997) Effects of docosahexaenoic acid on serum lipoproteinsin patients with combined hyperlipidemia: a randomized, double-blind, placebo-controlled trial. J. Am. Coll. Nutr. 16: 236–243.

50. Minihane, A. M., Khan, S., Leigh-Firbank, E. C., Talmud, P., Wright, J. W.,Murphy, M. C., Griffin, B. A. & Williams, C. M. (2000) ApoE polymorphism andfish oil supplementation in subjects with an atherogenic lipoprotein phenotype.Arterioscler. Thromb. Vasc. Biol. 20: 1990–1997.

51. Theobald, H. E., Chowienczyk, P. J., Whittall, R., Humphries, S. E. &Sanders, T. A. (2004) LDL cholesterol-raising effect of low-dose docosahexae-noic acid in middle-aged men and women. Am. J. Clin. Nutr. 79: 558–563.

52. Trinidad, T. P., Loyola, A. S., Mallillin, A. C., Valdez, D. H., Askali, F. C.,Castillo, J. C., Resaba, R. L. & Masa, D. B. (2004) The cholesterol-loweringeffect of coconut flakes in humans with moderately raised serum cholesterol.J. Med. Food 7: 136–140.

53. Romero, A. L., Romero, J. E., Galaviz, S. & Fernandez, M. L. (1998)Cookies enriched with psyllium or oat bran lower plasma LDL cholesterol innormal and hypercholesterolemic men from Northern Mexico. J. Am. Coll. Nutr.17: 601–608.

54. Gerhardt, A. L. & Gallo, N. B. (1998) Full-fat rice bran and oat bransimilarly reduce hypercholesterolemia in humans. J. Nutr. 128: 865–869.

55. Behall, K. M., Scholfield, D. J. & Hallfrisch, J. (1997) Effect of �-glucanlevel in oat fiber extracts on blood lipids in men and women. J. Am. Coll. Nutr. 16:46–51.

56. Kerckhoffs, D. A., Brouns, F., Hornstra, G. & Mensink, R. P. (2002)Effects on the human serum lipoprotein profile of �-glucan, soy protein andisoflavones, plant sterols and stanols, garlic and tocotrienols. J. Nutr. 132: 2494–2505.

57. Davidson, M. H., Dugan, L. D., Burns, J. H., Bova, J., Story, K. & Drennan,K. B. (1991) The hypocholesterolemic effects of beta-glucan in oatmeal andoat bran. A dose-controlled study. J. Am. Med. Assoc. 265: 1833–1839.

58. Katan, M. B., Grundy, S. M., Jones, P., Law, M., Miettinen, T. & Paoletti,R.; Stresa Workshop Participants. (2003) Efficacy and safety of plant stanolsand sterols in the management of blood cholesterol levels. Mayo. Clin. Proc. 78:965–978.

59. Ostlund, R. E. (2004) Phytosterols and cholesterol metabolism. Curr.Opin. Lipidol. 15: 37–41.

60. St-Onge, M. P. & Jones, P. J. (2003) Phytosterols and human lipidmetabolism: efficacy, safety, and novel foods. Lipids 38: 367–375.


by guest on Novem


Dow

nloaded from



Documents

Combination Between Nutrition and Exercise