Daily Apple versus Dried Plum: Impact on Cardiovascular Disease Risk Factors in Postmenopausal Women

RESEARCH Original Research

Daily Apple versus Dried Plum: Impact on Cardiovascular Disease Risk Factors in Postmenopausal Women Sheau C. Chai, PhD, RD; Shirin Hooshmand, PhD; Raz L. Saadat, MS, RD; Mark E. Payton, PhD; Kenneth Brummel-Smith, MD; Bahram H. Arjmandi, PhD, RD

ARTICLE INFORMATION Article history: Accepted 24 April 2012

Keywords: Apple consumption Cardiovascular health Copyright © 2012 by the Academy of Nutrition and Dietetics. 2212-2672/$36.00 doi: 10.1016/j.jand.2012.05.005

ABSTRACT Background Evidence suggests that consumption of apple or its bioactive components modulate lipid metabolism and reduce the production of proinflammatory molecules. However, there is a paucity of such research in human beings. Objective Women experience a lower rate of cardiovascular disease before menopause compared with men. However, after the onset of menopause, the risk of cardiovascular disease increases drastically due to ovarian hormone deficiency. Hence, we conducted a 1-year clinical trial to evaluate the effect of dried apple vs dried plum consumption in reducing cardiovascular disease risk factors in postmenopausal women. Design One-hundred sixty qualified postmenopausal women were recruited from the greater Tallahassee, FL, area during 2007-2009 and were randomly assigned to one of two groups: dried apple (75 g/day) or dried plum (comparative control). Fasting blood samples were collected at baseline, 3, 6, and 12 months to measure various parameters. Physical activity recall and 7-day dietary recall were also obtained. Results Neither of the dried fruit regimens significantly affected the participants’ reported total energy intake throughout the study period. On the contrary, women who consumed dried apple lost 1.5 kg body weight by the end of the study, albeit not significantly different from the dried plum group. In terms of cholesterol, serum total cholesterol levels were significantly lower in the dried apple group compared with the dried plum group only at 6 months. Although dried plum consumption did not significantly reduce serum total cholesterol and low-density lipoprotein cholesterol levels, it lowered their levels numerically by 3.5% and 8%, respectively, at 12 months compared with baseline. This may explain the lack of significance observed between the groups. However, within the group, women who consumed dried apple had significantly lower serum levels of total cholesterol and low-density lipoprotein cholesterol by 9% and 16%, respectively, at 3 months compared with baseline. These serum values were further decreased to 13% and 24%, respectively, after 6 months but stayed constant thereafter. The within-group analysis also reported that daily apple consumption profoundly improved atherogenic risk ratios, whereas there were no significant changes in lipid profile or atherogenic risk ratios as a result of dried plum consumption. Both dried fruits were able to lower serum levels of lipid hydroperoxide and C-reactive protein. However, serum C-reactive protein levels were significantly lower in the dried plum group compared with the dried apple group at 3 months. Conclusions There were no significant differences between the dried apple and dried plum groups in altering serum levels of atherogenic cholesterols except total cholesterol at 6 months. However, when within treatment group comparisons are made, consumption of 75 g dried apple (about two medium-sized apples) can significantly lower atherogenic cholesterol levels as early as 3 months. Furthermore, consumption of dried apple and dried plum are beneficial to human health in terms of anti-inflammatory and antioxidative properties. J Acad Nutr Diet. 2012;112:1158-1168.

C

ARDIOVASCULAR DISEASE (CVD) IS A MAJOR PUBLIC health threat because CVD is the number-one killer in the United States. According to the American Heart Association, approximately 400,000 men and 440,000 women died as result of CVD in 2006, and currently about 81 million Americans are diagnosed with CVD.1 In 2008, 1158

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the direct and indirect cost for CVD was $475.3 billion,1 and this amount continues to rise. A fall in estrogen levels in postmenopausal women is associated with unfavorable changes in lipid profiles, including low-density lipoprotein (LDL) cholesterol, triglycerides (TG), and total cholesterol,2-4 and increases the production of proinflammatory molecules5,6 and © 2012 by the Academy of Nutrition and Dietetics.

RESEARCH Table 1. Nutrient concentration of dried apple and dried plum obtained by both calculation and actual analyses Dried Apple (per 75 g)

Dried Plum (per 100 g)

Nutrient

Calculated

Actual

Calculateda

Actualb

Energy (kcal)

240

219

239

220

Fat (g) Total carbohydrates (g)

a

0.43 58.5

Fiber (g)

6

Protein (g)

1.5

b

0.37 70.5 Not assessed 0.83

0.52 62.7 7.10 2.61

0.23 63.4 Not assessed 2.24

a

Results obtained from Food Processor version 7.50 (ESHA Research). Gross energy analyzed by bomb calorimetry (Parr 1261 Calorimeter, Parr Instrument Co), crude protein by the Association of Analytical Communities Kjeldahl method, and fat by ester extraction.

b

oxidative stress markers7,8 placing them at a higher risk for CVD. Although hyperlipidemia is often treated with cholesterol-lowering drugs such as statins, these drugs are not only associated with certain risks; for example, liver damage and muscle weaknesses,9 but they are also costly. For instance, the estimated cost for statin drugs in the United States was $15.5 billion in 2004.10 Factors leading to CVD include hyperlipidemia, hypertension, insulin resistance, and inflammation. Estrogen deficiency may affect a number of the aforementioned factors and hence may be considered a risk factor for the development of CVD. Although hormone therapy can lower some of these risk factors, it is believed that the risk associated with hormone therapy outweigh its benefits.11,12 As a result, postmenopausal women continue to seek alternative and more natural ways to decrease CVD risk associated with menopause. Animal and human research studies have shown that bioactive constituents of certain foods such as polyphenolic compounds and fiberarebeneficialindecreasingCVDrisk.13-17 Amongfruits,apples are an excellent source of soluble fiber, pectin, and polyphenolic compounds.18,19 The polyphenols present in apple include quercetin, catechin, phloridzin, and chlorogenic acid and are ranked the second highest in antioxidant properties among all commonly consumed fruits and vegetables in the United States.20 Apple or its bioactive compounds have been reported to inhibit cancer cell proliferation, decrease lipid oxidation, and lower total and LDL cholesterol levels and has also been reported to have antioxidative and anti-inflammatory properties.21,22 It was hypothesized that regular intake of apple favorably improves lipid profiles, reduces atherogenic risk ratios, lowers C-reactive protein (CRP) levels, and decreases levels of oxidative stress marker in postmenopausal women. If long-term apple consumption is shown to effectively lower CVD risks in postmenopausal women, it would provide postmenopausal women with a relatively inexpensive and feasible dietary means for promoting their cardiovascular health.

METHODS Participants and Study Design A total of 236 healthy postmenopausal women (1 to 10 years past menopause), not receiving hormone therapy and other pharmacologic agents, including cholesterol-lowering drugs, for at least 3 months before the study were screened and recruited from Tallahassee, FL, and surrounding areas. ParticiAugust 2012 Volume 112 Number 8

pants with metabolic bone disease, renal disease, a history of urolithiasis, cancer, CVD, diabetes mellitus, respiratory disease, gastrointestinal disease, liver disease, and other chronic diseases and heavy smokers (⬎20 cigarettes/day) were excluded. The study protocol was approved by the Institutional Review Board at The Florida State University. After an initial prescreening over the telephone, qualified participants were invited to the study site for their first visit. During the first visit, written informed consent was obtained from all participants. A complete medical and nutrition history was obtained from participants by a registered dietitian for screening purposes. Based on inclusion and exclusion criterion, a total of 160 postmenopausal women qualified and participated in the study. The participants were advised to maintain their usual physical activity and diet pattern. Eligible participants were randomly assigned to one of the two dietary intervention groups by using a pregenerated randomization list: dried apple (75 g) or comparative control (100 g dried plum). The rationale for choosing the dose of dried apple was based on our earlier short-term clinical trial (B. H. Arjmandi, PhD, RD, and D. A. Khalil, PhD, unpublished data, May 2002). In that study, dried apple was well tolerated by postmenopausal women and positively influenced lipid profiles. The amount of dried plum chosen was based on comparable amount of energy, carbohydrates, fat, and fiber that would be obtained from 75 g dried apple (Table 1). Participants were not blinded to intervention. However, researchers and personnel, including the statistician were blinded to the intervention groups when running the assays and analyzing the data. Participants were given customized calendars and were asked to mark the days they missed consuming the study regimen and record and/or return any unused portion for compliance monitoring purposes.

Dietary and Physical Activity Assessments and Anthropometry Measurements A 7-day dietary recall was collected from all participants by a registered dietitian at baseline, 3, 6, and 12 months. Collected dietary recalls were analyzed using Food Processor SQL Nutrition and Fitness Program (ESHA Research). With the exception of height measured at baseline, body weights were repeatedly measured at baseline, 3, 6, and 12 months. Another confounding factor, physical activity that has been known to influence lipid metabolism was assessed using the Five-City Project Physical Activity Recall.23 The JOURNAL OF THE ACADEMY OF NUTRITION AND DIETETICS

1159

RESEARCH Assessed for eligibility (n=236)

Excluded (n=76) Not mee
ng inclusion criteria (n=70) Enrollment (n=160)

Alloca
on

Dried Apple

Dried Plum

Allocated to interven
on (n=72) Discon
nued interven
on (n=13): Non-compliance, GIa issues, headache, and personal reasons

Allocated to interven
on (n=88) Discon
nued interven
on (n=24): Non-compliance, GIa issues, gallbladder disease, and received HTb treatment

3 Month Follow-up Con
nued interven
on (n=59) Discon
nued interven
on (n=10):Non-compliance, health related, personal reasons

3 Month Follow-up Con
nued interven
on (n=64) Discon
nued interven
on (n=4: Non-compliance, personal reasons

6 Month Follow-up Con
nued interven
on (n=49) Discon
nued interven
on (n=10): Non-compliance, personal reasons

6 Month Follow-up Con
nued interven
on (n=60) Discon
nued interven
on (n=5): Non-compliance, personal reasons

1 Year Analysis Analyzed (n=45) Excluded from analysis (n=0)

1 Year Analysis Analyzed (n=55) Excluded from analysis (n=0)

Figure 1. Flow chart of the study design and subject participation. aGI⫽gastrointestinal. bHT⫽hormone therapy. Five-City Project Physical Activity Recall was used to assess current physical activity, sleep, and activity pattern, including leisure, occupational, and home activities. This 7-day activity recall has been used in cross-sectional designs and community health surveys24 and has been validated by Taylor and colleagues25 and Elmore.26 The physical activity assessment was also collected at baseline, 3, 6, and 12 months. 1160

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Analysis of Lipid Profiles and Atherogenic Risk Ratios Fasting venous blood for plasma and serum was collected between 8 and 10 AM on a designated date from each participant in vacutainers with appropriate anticoagulants at baseline, 3, 6, and 12 months. Serum and plasma were separated by cenAugust 2012 Volume 112 Number 8

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851.1⫾56.6 There were no statistical significant differences observed between baseline values of the treatment groups and between baseline, 3 mo, 6 mo, and 12 mo corresponding values.

a

25.2⫾4.8 —

821.3⫾43.6 826.1⫾35.8

— 24.9⫾4.6

795.1⫾38.7 829.4⫾60.5

24.2⫾4.0 —

896.2⫾52.8 958⫾57.1

— 24.8⫾4.1

919.5⫾52.5 Physical activity (kcal/d)

Body mass index

163.1⫾5.5

66.8⫾13.2 66.2⫾11.4

— —

67.7⫾12.6 66.3⫾12.2

163.1⫾5.4 165.8⫾5.2

66.8⫾12.3 67.6⫾11.7

— —

69.4⫾13.1 68.3⫾12.0

165.9⫾5.3

Weight (kg)

Height (cm)

—

— —

— —

— 57.5⫾4.01

6.12⫾3.45 —

— —

— — 6.09⫾4.0

— 55.6⫾5.0

12 mo 6 mo 12 mo

Baseline

3 mo

Dried Plum

4™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™ mean⫾standard error ™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™3

Age (y)

Of the 160 postmenopausal women, 100 (45 in the dried apple group and 55 in the dried plum group) completed the study (Figure 1). By the end of the study, the attrition rates were not significantly different between the two interventions (37.5%). The common reasons that participants were unable to finish the study included noncompliance with the study protocol, claims of medical and health related conditions, and personal reasons such as traveling, moving, family issue, and lack of

Time since menopause (y)

RESULTS Baseline Characteristics, Anthropometric Measurements, Dietary Intakes, and Physical Activity Assessments

6 mo

Statistical analysis was performed using analysis of variance methods with PROC MIXED in PC SAS (version 9.1, 2006, SAS Institute) to determine the main and interaction effects of intervention (dried apple or dried plum), and time (baseline, 3, 6, and 12 months). A split plot model of repeated measures was used for statistical analysis both within and between treatment groups. The mean changes in outcome variables during the intervention periods were compared by analyzing interaction effects of intervention and time, using the SLICE option in an LSMEANS statement. Data are reported as least square mean⫾standard error. In all statistical comparisons, differences with P⬍0.05 were considered significant.

3 mo

STATISTICAL METHODS

Baseline

CRP, a marker of inflammation was assessed at baseline, 3, 6, and 12 months using the SIRRUS Clinical Chemistry (Stanbio Laboratory). Serum levels of lipid hydroperoxide (LPO) were also assessed at baseline, 3, 6, and 12 months using colorimetric methods (Cayman Chemicals). Before performing the assay, serum samples were extracted in chloroform to prevent the presence of hydrogen peroxide that were found in many biological samples, which readily reacts with ferrous ions causing an overestimation of LPO. Chloroform extract of serum samples were added to chloroform-methanol solvent and then mixed well with freshly prepared chromogen reagent. After incubating for 5 minutes at room temperatures, samples were read at 500 nm.

Measure

Measurement of Inflammatory and Oxidative Stress Markers

Dried Apple

trifuging at 4,000 rpm for 15 minutes at 4⬚C within 2 hours of collection using an IEC CL31R multispeed centrifuge (Thermo Electron Corporation). Samples were then aliquoted and stored at ⫺80⬚C until analyses. Serum was analyzed for total cholesterol, high-density lipoprotein (HDL) cholesterol, and TG in duplicate at baseline, 3, 6, and 12 months according to the enzymatic method and trinder color system.27-29 The intensity of the color mixture produced was read at 500 nm using Ultrospec 2100 Pro UV/Visible Spectrophotometer (GE Healthcare Life Sciences). All lipid reagents, including total cholesterol, HDL cholesterol, and TG were purchased from Pointe Scientific, Inc. After determining serum total cholesterol, HDL cholesterol, and TG levels, serum LDL cholesterol level was calculated using the Friedewald equation30: LDL cholesterol⫽total cholesterol–HDL cholesterol–(0.20⫻TG). The atherogenic risk ratios were calculated as follows: total cholesterol/HDL cholesterol, LDL cholesterol/HDL cholesterol, and HDL cholesterol/LDL cholesterol.

Table 2. Characteristics of study participants and physical activity patterns assessed in a 1-year clinical trial to evaluate the effect of dried apple vs dried plum consumption in reducing cardiovascular disease risk factors in postmenopausal womena

RESEARCH

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Dried Apple Daily intake

Baseline

3 mo

6 mo

Dried Plum 12 mo

Baseline

3 mo

6 mo

12 mo

4™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™ mean⫾standard error ™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™ 3 Total energy (kcal)

1,680⫾56

1,747⫾73

1,707⫾81

1,805⫾64

1,645⫾69

1,791⫾61

1,833⫾85

1,847⫾77

Protein (g)

72.5⫾3.0

66.7⫾2.7

67.2⫾3.5

73.6⫾2.8

67.0⫾2.7

72.8⫾2.8

68.8⫾2.6

72.5⫾3.2

Carbohydrate (g)

212⫾8

236⫾10

227⫾9

231⫾9

205⫾10

233⫾9

256⫾17

233⫾10

Dietary fiber (g)

21.2⫾1.2

24.5⫾1.1

22.7⫾1.2

25.0⫾1.4

21.2⫾1.1

24.4⫾1.3

26.6⫾1.8

26.2⫾1.7

Total fat (g)

61.1⫾3.2

60.9⫾4.8

60.9⫾4.6

67.1⫾3.9

62.3⫾3.1

63.8⫾3.1

60.5⫾2.7

70.7⫾4.6

Saturated fat (g)

18.8⫾1.0

20.6⫾2.5

19.8⫾1.7

21.0⫾1.2

19.2⫾1.3

19.7⫾1.1

19.2⫾1.0

21.7⫾1.4

Monounsaturated fat (g)

21.4⫾1.5

19.4⫾1.4

20.6⫾1.8

22.8⫾1.8

21.8⫾1.2

21.3⫾1.2

20.5⫾1.1

23.4⫾1.8

Polyunsaturated fat (g)

11.6⫾0.9

11.0⫾0.8

11.1⫾0.9

12.7⫾1.1

11.6⫾0.6

11.7⫾0.7

11.2⫾0.7

13.9⫾1.1

0.5⫾0.1

0.4⫾0.1

0.4⫾0.1

0.8⫾0.1

0.4⫾0.1

0.8⫾0.2

0.7⫾0.1

0.8⫾0.2

196.5⫾14.5

195.9⫾15.8

227.2⫾18.0

221.4⫾14.0

202.5⫾12.5

224.8⫾13.3

223.9⫾12.3

249.1⫾17.4

Vitamin A (IU)

11,533⫾876

8,954⫾720

9,129⫾959

11,354⫾1,218

10,712⫾923

11,526⫾992

10,137⫾816

Vitamin C (mg)

107⫾8

93⫾8

82⫾8

93⫾7

Vitamin D (IU)

103⫾11

107⫾11

101⫾10

Vitamin E (IU)

5.6⫾0.5

6.7⫾0.5

6.0⫾0.6

Vitamin K (␮g)

115.6⫾11.6

168.0⫾16.8

135.0⫾27.3

Macronutrients

Trans fat (g) Total cholesterol (mg) Vitamins

93⫾8

95⫾11

105⫾12

97⫾12

7.5⫾0.8

8.6⫾1.8

174.5⫾30.5

209.2⫾21.6

12,926⫾1410

98⫾12

99⫾68

100⫾11

96⫾10

102⫾101

7.4⫾0.7

7.2⫾0.6

8.9⫾1.3

170.4⫾17.3

178.0⫾16.6

198.4⫾21.8

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Minerals (mg) Calcium

808⫾47

896⫾52

806⫾57

861⫾54

927⫾142

779⫾62

762⫾42

885⫾63

Iron

14.7⫾1.2

14.4⫾0.9

13.5⫾0.7

14.9⫾0.9

16.8⫾2.5

15.0⫾1.0

15.0⫾0.9

15.7⫾1.2

Magnesium

245⫾10

288⫾12

263⫾16

301⫾17

296⫾13

285⫾14

310⫾19

321⫾21

Phosphorus

997⫾42

1172⫾53

1048⫾63

1155⫾49

1120⫾50

1079⫾51

1087⫾44

1161⫾64

2,810⫾115

2,643⫾129

2,916⫾121

2,957⫾131

2,687⫾144

3,030⫾147

3,025⫾149

Potassium Zinc a

2,661⫾97 7.1⫾0.3

8.2⫾0.4

7.4⫾0.4

8.6⫾0.4

10.1⫾2.0

There were no statistical significant differences observed between baseline values of the treatment groups and between baseline, 3 mo, 6 mo, and 12 mo corresponding values.

7.5⫾0.3

8.2⫾0.5

8.1⫾0.4

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1162

Table 3. Daily nutrient intake calculated from 7-day dietary recall of women at baseline, 3 mo, 6 mo, and 12 mo of supplementation with 75 g dried apple or 100 g dried plum dailya

RESEARCH

Figure 2. Mean serum total cholesterol at baseline, 3 months (3M), 6 months (6M), and 12 months (12M) in postmenopausal women consuming dried plum or dried apple. Bars represents mean⫾standard error of the mean.*Significant difference at P⬍0.05 in comparison with baseline dried apple. **Significant difference at P⬍0.05 in comparison with intervention groups at 6 months. To convert mg/dL cholesterol to mmol/L, multiply mg/dL by 0.026. to convert mmol/L cholesterol to mg/dL, multiply mmol/L by 38.6. Cholesterol of 193 mg/dL⫽5.00 mmol/L. motivation. The compliance to the dried fruit regimens in those participants who completed the study was on average 82% for each group. Baseline characteristics of participants including age, time since menopause, and body mass index (Table 2) did not significantly differ between the two groups. The mean body weights of the participants in both groups were not significantly different at baseline, 3, 6, and 12 months. However, 12 months of apple consumption resulted in 1.5 kg weight loss compared with baseline. Analysis of the 7-day dietary recall and physical activity recall reported that the participant’s food intakes (Table 3) and physical activity levels (Table 2) were not significantly different between baseline values of the two intervention groups and between any time points throughout the study.

lesterol increased numerically by 3% and TG decreased numerically by 9% after 12 months’ consumption of dried apple in postmenopausal women (Table 4). There were no significant differences in total cholesterol: HDL cholesterol and LDL:HDL cholesterol ratios between the dried apple and dried plum group except at baseline. Ratios of total cholesterol:HDL cholesterol and LDL:HDL cholesterol significantly decreased with 3 months of consumption of dried apple and both of these ratios remained the same thereafter (Figures 4 and 5). Daily consumption of dried apple also tended to increase ratio of HDL:LDL cholesterol with a P value of 0.0780 (Table 4). There were no significant changes in atherogenic risk ratios of total cholesterol:HDL cholesterol, LDL:HDL cholesterol, and HDL:LDL cholesterol as a result of dried plum consumption.

Lipid Profiles and Atherogenic Risk Ratios

CRP and Oxidative Stress Markers

Serum total cholesterol levels were significantly lower in the dried apple group compared with the dried plum group at 6 months, but not at 3 or 12 months. In terms of serum levels of LDL cholesterol, there were no significant differences between the dried apple and dried plum group. However, within the treatment group analysis, 3 months’ consumption of dried apple significantly reduced serum total and LDL cholesterol by 9% and 16%, respectively, and the levels of serum total and LDL cholesterol further reduced to 13% and 24%, respectively, after 6 months’ consumption of dried apple compared with baseline, then remained the same at 12 months (Figures 2 and 3). Dried plum consumption reduced serum total and LDL cholesterol by 3.5% and 8%, respectively, at 12 months compared with baseline, but the decline was not statistically significant. With respect to serum levels of HDL cholesterol and TG, there were no statistically significant changes between the groups and within the groups. However, serum HDL choAugust 2012 Volume 112 Number 8

Serum CRP levels were significantly lower in the dried plum group compared with the dried apple group at 3 months but not at 6 or 12 months. Serum CRP levels began to noticeably decrease by 22% in the dried apple group after 6 months and the level of serum CRP further decreased by 32% by the end of the study (Table 5). On the other hand, serum CRP levels decreased by 17% in the dried plum intervention group after 3 months, then remained the same thereafter. Twelve months of consumption of either dried apple or dried plum reduced serum levels of lipid hydroperoxide by 33% and 38%, respectively, in postmenopausal women (Table 5).

DISCUSSION There are a number of studies31,32 demonstrating that regular consumption of fruits and vegetables improves dyslipidemia. Diets rich in fiber, particularly soluble dietary fibers such as pectin, psyllium, and oat bran, have proven to be effective in JOURNAL OF THE ACADEMY OF NUTRITION AND DIETETICS

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Figure 3. Mean serum low-density lipoprotein (LDL) cholesterol at baseline, 3 months (3M), 6 months (6M), and 12 months (12M) in postmenopausal women consuming dried plum or dried apple. Bars represent mean⫾standard error of the mean. *Significant difference at P⬍0.05 in comparison with baseline dried apple. To convert mg/dL cholesterol to mmol/L, multiply mg/dL by 0.026. to convert mmol/L cholesterol to mg/dL, multiply mmol/L by 38.6. Cholesterol of 193 mg/dL⫽5.00 mmol/L.

Table 4. Effects of dried apple and dried plum on high-density lipoprotein (HDL) cholesterol, triglycerides (TG), and HDL: low-density lipoprotein (LDL) ratio in postmenopausal womena Dried Apple Measure

Baseline

3 mo

6 mo

Dried Plum 12 mo

P value

4™™™™™™™™™ mean⫾standard error ™™™™™™™3 HDL (mg/dL)b c

TG (mg/dL) HD:LDL

Baseline

3 mo

6 mo

12 mo

P value

4™™™™™™™™™ mean⫾standard error ™™™™™™™3

62⫾2.3

64⫾2.2

62⫾2.3

64⫾2.8

0.8603

67⫾2.1

68⫾2.0

68⫾2.0

67⫾2.2

0.9763

115⫾5.7

110⫾5.2

118⫾6.8

104⫾5.0

0.3130

103⫾3.3

106⫾4.4

111⫾5.1

111⫾4.6

0.5508

0.7⫾0.06

0.8⫾0.09

0.9⫾0.08

0.9⫾0.10 0.0780

0.8⫾0.07

0.8⫾0.06

0.8⫾0.05

0.9⫾0.08 0.8079

a

There were no statistical significant differences observed between baseline values of treatment groups and between baseline, 3 mo, 6 mo, and 12 mo corresponding values. To convert mg/dL cholesterol to mmol/L, multiply mg/dL by 0.026. To convert mmol/L cholesterol to mg/dL, multiply mmol/L by 38.6. Cholesterol of 62 mg/dL⫽1.61 mmol/L. c To convert mg/dL triglyceride to mmol/L, multiply mg/dL by 0.0113. To convert mmol/L cholesterol to mg/dL, multiply mmol/L by 88.6. Triglyceride of 115 mg/dL⫽12.99 mmol/L. b

reducing serum cholesterol levels in both human beings33,34 and animals.13,14,35 Dietary fiber lowers cholesterol by several mechanisms, including enhanced fecal excretion of sterols and increased conversion of cholesterol to bile acids.36 Apple consumption, including fresh apple,37,38 apple juice,39,40 apple extracts,41 apple polyphenols,42-44 or apple pectin18,19,45 have been reported to exert cardioprotective effects in various animal models. Most of these studies have concluded that the health benefits of apple consumption may be related to any of its components, including fiber and phytochemicals. However, findings from these studies cannot be directly extrapolated to human beings. Therefore, clinical trials examining the health benefits of apple consumption are necessary to confirm that people with a higher intake of apples experience a reduced risk of CVD. To our knowledge, this is the first clinical trial to investigate the effects of 1 year of apple consumption (in a dried form) in reducing CVD risk factors, including body weight, lipid profiles, atherogenic risk ratios, and inflammatory and oxidative stress markers in postmenopausal women. 1164

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We began with 160 participants and of these, 100 individuals successfully completed the intervention of consuming either dried apples or dried plums daily for 12 months. Of women who completed the study, the compliance for each group was approximately 82%. It is important to note that the dried plums were used as a comparative control group due to a similar nutritional composition to dried apples as well as the known cardioprotective effects observed in a previous study.15 Dried plums contain a number of phenolic compounds as well as ascorbic acid and carotenoids46 that may exert positive effects on lipid metabolism. Our findings suggest that daily incorporation of dried fruits (both apple and plum) into a diet, without intentional dietary modifications during the study, do not significantly affect the total energy intake or physical activity patterns of postmenopausal women. In addition, the dried apple group displayed a 1.5 kg decrease in body weight from baseline to the final time point despite the additional energy intake from the dried apples. It is possible that participants may have altered their dietary intake to compensate for the dried fruit regimen deAugust 2012 Volume 112 Number 8

RESEARCH

Figure 4. Mean ratio of total cholesterol to high-density lipoprotein cholesterol at baseline, 3 months (3M), 6 months (6M), and 12 months (12M) in postmenopausal women consuming dried plum or dried apple. Bars represent mean⫾standard error of the mean. *Significant difference at P⬍0.05 in comparison with baseline dried apple. **Significant difference at P⬍0.05 in comparison with intervention groups at baseline.

Figure 5. Mean ratio of low-density to high-density lipoprotein cholesterol at baseline, 3 months (3M), 6 months (6M), and 12 months (12 M) in postmenopausal women consuming dried plum or dried apple. Bars represent mean⫾standard error of the mean. *Significant difference at P⬍0.05 in comparison with baseline dried apple. **Significant difference at P⬍0.05 in comparison with intervention groups at baseline. spite instructions to maintain constant dietary patterns. However, dried apples are rich in soluble fiber and pectin, known to suppress food intake and thereby decrease body weight.37,47,48 This may also explain, in part, the observed decrease in body weight within this group. Evidence suggests that increased levels of LDL cholesterol and higher atherogenic risk ratios including total cholesterol: HDL cholesterol and LDL:HDL cholesterol are associated with increased risks of CVD events and atherosclerosis.49,50 Our findings demonstrated that there were no significant differAugust 2012 Volume 112 Number 8

ences between the dried apple and dried plum group with respect to serum levels of LDL cholesterol, HDL cholesterol, or TG. However, the dried apple group did display significantly lower serum total cholesterol levels at the 6-month time point when compared with the dried plum group. These findings were not observed at the 3- or 12-month time points. Within the dried apple group, serum total and LDL cholesterol significantly decreased by 9% and 16%, respectively, after 3 months of dried apple consumption when compared with baseline values. Furthermore, a 13% decrease in total cholesJOURNAL OF THE ACADEMY OF NUTRITION AND DIETETICS

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RESEARCH Table 5. Effects of dried apple and dried plum on C-reactive protein (CRP) and lipid hydroperoxide (LPO) in postmenopausal women Dried Apple Measure

Baseline

3 mo

6 mo

Dried Plum 12 mo

P value Baseline

4™™™™™™™™™ mean⫾standard error ™™™™™™™3 CRP (mg/dL)a

LPO (␮mol/L) 58.9⫾6.4 46.7⫾8.3

xy

x

y

6 mo

12 mo

P value

4™™™™™™™™™ mean⫾standard error ™™™™™™™™ 3

2.1⫾0.41 2.1⫾0.38* 1.6⫾0.38 1.4⫾0.72 0.0187 x

3 mo

59.1⫾4.0 39.2⫾4.0 0.0218

1.8⫾0.60 52.4⫾5.8

xy

1.5⫾0.37* 1.6⫾0.37 1.4⫾0.77 yz

40.0⫾8.7

0.0187

60.3⫾3.4 32.6⫾3.9 ⬍0.0001 x

z

a

To convert mg/dL C-reactive protein to nmol/L, multiply mg/dL by 0.9524. To convert nmol/L C-reactive protein to mg/L, multiply nmol/L by 1.05. C-reactive protein of 2.1 mg/dL⫽2.00 nmol/L. xyz Within a row, means that do not share the same superscript (x, y, z) are significantly different from each other at P⬍0.05. *Denotes a significant difference in comparison with intervention groups at 3 mo (P⬍0.05).

terol and a 24% decrease in LDL cholesterol were observed after 6 months consumption of dried apple when compared with baseline values and thereafter values remained constant. It is important to note that though there was a decrease in total and LDL cholesterol of 3.5% and 8%, respectively, in the dried plum group from baseline to the 12-month time point, these values were not statistically significant. Although LDL cholesterol and total cholesterol levels were significantly decreased within the dried apple group, changes in serum HDL cholesterol from baseline to the 3-, 6-, and 12-month time points were not significant. However, HDL cholesterol did increase numerically by 3% along with a 9% decrease in TG after 12 months of dried apple consumption. These alterations are of important clinical relevance with respect to natural methods of improving blood lipid profiles. In addition, the atherosclerosis risk ratios of total cholesterol:HDL cholesterol and LDL:HDL cholesterol significantly decreased by 15% and 21%, respectively, within the dried apple group, whereas no significant changes were observed within the dried plum group. Yet, the dried plum ratios were significantly lower at baseline than the dried apple ratios, which lessen the influence of these findings for which we cannot offer an explanation. Despite this discrepancy, the significant decreases observed in the dried apple group for the risk ratios are of clinical relevance and importance. Furthermore, the structure and chemical composition of pectin differs among plants and one explanation for the cholesterol-lowering properties of apple may be due to its unique pectin composition known to drastically increase fecal excretion of bile salts, thereby reducing cholesterol.13,14 Another health benefit of apple may be through its ability to lower CRP levels. Elevated serum levels of CRP have been implicated in many chronic diseases, including CVD. More recently, CRP has been identified as a major contributor and predictor of the development of atherosclerosis, CVD complications, and diabetes.51 Our findings demonstrate that both dried apples and dried plums were able to lower serum CRP levels. Dried plum group was able to reduce CRP levels by 17% within 3 months, whereas this decrease was not observed in the dried apple group until the 6-month time point. However, CRP levels remained constant in the dried plum group from the 3-month to the 12month time point, whereas 12 months’ consumption of dried apple reduced CRP levels by 32%, an additional 15% from the 3-month values. Although these findings are not statistically significant, they do merit clinical relevance and do suggest that 1166

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dried plums may have a more rapid effect in lowering the production of certain inflammatory markers but a lower effect overall, when consumed for 1 year compared with dried apple consumption. Hence, from our observation, it can be suggested that both dried fruit regimens lower serum CRP levels, albeit the dried plum group displays a quicker decrease whereas the dried apple group displays a greater decrease overall. Cardiovascular health also, in part, depends on oxidative status. Oxidized lipids may be important mediators of lipid peroxidation and are known to initiate foam cell formation that accelerates the process of plaque formation.52,53 In our study, 12-month consumption of dried apple significantly reduced serum levels of LPO by 33%. Although dried plum consumption did not have significant effects on serum lipid profile and atherogenic risk ratios, it also exhibited a potent antioxidative property as evidenced by reducing the mean serum LPO level by 38%. In terms of limitations, the participants in our study were a specific population of postmenopausal women; therefore, the effectiveness of these dried fruits in improving lipid profiles, indexes of oxidative stress, and inflammation should be examined in both men and women of different ages. Another limitation of this study was that the participants were not blinded to the interventions. To minimize the bias, the participants were not told what they should expect as results. Furthermore, the research assistants, laboratory technicians, and the statistician were blinded to the nature of interventions when running the assays and analyzing the data. The attrition rate of 37.5% for both groups is considered high; hence, additional studies are needed to show whether consumption of lower quantities of dried apple and/or less frequent consumption would have the same effect.

CONCLUSIONS By comparing all the pros and cons between medications and functional foods in the context of cardiovascular health, our findings show that daily incorporation of dried apple into diets favorably improves cardiovascular health in postmenopausal women. In terms of between-groups comparison, there were no significant differences between the dried apple and dried plum groups in serum levels of atherogenic cholesterols except total cholesterol at 6 months. However, withingroup analysis reported that dried apple consumption results in significantly lower atherogenic cholesterol levels as early as 3 months. Although dried plum consumption did not significantly influence lipid profile and atherogenic risk ratios, August 2012 Volume 112 Number 8

RESEARCH one cannot rule out its health benefits because dried plums are also rich in polyphenolic compounds known to exert antioxidative and anti-inflammatory effects.

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AUTHOR INFORMATION S. C. Chai is a postdoctoral research associate, Nutrition Research Institute, The University of North Carolina at Chapel Hill; at the time of the study, she was a doctoral research assistant, Department of Nutrition, Food and Exercise Sciences, The Florida State University, Tallahassee. S. Hooshmand is an assistant professor, The School of Exercise and Nutritional Sciences, San Diego State University, San Diego, CA; at the time of the study, she was a doctoral research assistant, Department of Nutrition, Food and Exercise Sciences, The Florida State University, Tallahassee. R. L. Saadat is a registered dietitian, Weight Loss Centers, Beverly Hills, CA; at the time of the study, she was a master’s level research assistant, Department of Nutrition, Food and Exercise Sciences, The Florida State University, Tallahassee. M. E. Payton is a professor, Department of Statistics, Oklahoma State University, Stillwater. K. Brummel-Smith is professor and chair, Department of Geriatrics, College of Medicine, and B. H. Arjmandi is professor and chair, Department of Nutrition, Food, and Exercise Sciences, and director for the Center for Advancing Exercise and Nutrition Research on Aging, The Florida State University, Tallahassee. Address correspondence to: Bahram H. Arjmandi, PhD, RD, Department of Nutrition, 436 Sandels Bldg, The Florida State University, Tallahassee, FL 32306. E-mail: [email protected]

STATEMENT OF POTENTIAL CONFLICT OF INTEREST No potential conflict of interest was reported by the authors.

FUNDING/SUPPORT This study was partly supported by the National Research Initiative of the US Department of Agriculture Cooperative State Research, Education, and Extension Service (grant no. 2005-35200-17053).

ACKNOWLEDGEMENTS The authors thank the California Dried Plum Board for providing the dried plums used in the study.

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