Reviews in Cardiovascular Medicine, 2021, 22(3): 835-843 DOI: 10.31083/j.rcm2203089

Systematic Review

Apple or apple polyphenol consumption improves cardiovascular disease risk factors: a systematic review and meta-analysis

Xiaoqing Zhu1,, Guanhua Xu1,, Wangyan Jin1, Yingying Gu1, Xuhua Huang1, Lidan Ge,2,*

1Department of Critical Medicine, The First People’s Hospital of Xiaoshan District, 311200 Hangzhou, Zhejiang, China

2Department of Geriatrics, The First People’s Hospital of Xiaoshan District, 311200 Hangzhou, Zhejiang, China

*Corresponding Author(s): gelidan0571@126.com (Lidan Ge)

First author contact:

These authors contributed equally.

Academic Editor: Demosthenes B Panagiotakos
This article belongs to the Special Issue: Diet, nutrients and cardiovascular disease prevention (https://rcm.imrpress.com/EN/subject/listSubjectChapters.do?subjectId=1615942769352).

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Copyright:  ©2021  The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license ( https://creativecommons.org/licenses/by/4.0/).

Abstract

Many fruits and vegetables have been found to have a protective effect against cardiovascular diseases. We conducted a systematic review and meta-analysis to determine the relationship between apple or apple polyphenol intake and cardiovascular disease risk. The PubMed, Embase, Cochrane, and Web of Science databases were searched up to August 4, 2020. Studies that had an intervention time of >1 week; used apple or apple polyphenols as the intervention; were designed as a randomized controlled trial; and measured blood pressure, cholesterol, and blood glucose levels were included. The meta-analysis showed that the group with apple or apple polyphenol intake had significantly higher high-density lipoprotein levels (standardized mean difference [SMD] = 0.34, 95% confidence interval [CI] [0.01, 0.67], p = 0.0411, I2 = 77%, random-effects model) and significantly lower C-reactive protein levels (SMD = –0.43, 95% CI [–0.65, –0.20], p = 0.0002, I2 = 18%, fixed-effects model) than the control group, indicating that the intervention reduced the risk of cardiovascular diseases. Apple or apple polyphenol intake is associated with a reduced risk of cardiovascular diseases. These results are consistent with the old saying that eating an apple a day can help keep the doctors away.

Keywords: Apples; Apple polyphenols; Cardiovascular disease; Blood pressure; Cholesterol level; Blood glucose level

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Cite this article

Xiaoqing Zhu, Guanhua Xu, Wangyan Jin, Yingying Gu, Xuhua Huang, Lidan Ge. Apple or apple polyphenol consumption improves cardiovascular disease risk factors: a systematic review and meta-analysis. Reviews in Cardiovascular Medicine, 2021, 22(3): 835-843 doi:10.31083/j.rcm2203089

1. Introduction

According to the World Health Organization, cardiovascular diseases (CVDs) are currently the leading cause of death worldwide [1]. High blood pressure, smoking habit, high cholesterol level, diabetes, overweight or obesity, and a sedentary lifestyle can all negatively influence cardiovascular health. Population-wide strategies to address behavioral risk factors such as an unhealthy diet and obesity can help prevent most CVDs. Some studies have shown that the consumption of plant products such as fruits and vegetables is associated with a reduction in the risk of CVD development [2]. Moreover, some studies proposed that the intake of certain single nutrients (such as vitamin C) at the level naturally present in plants is related to a reduction of disease risk; however, these associations cannot explain the protective effect of plant foods on health [2]. Therefore, it is speculated that other nonnutritive components in plants, such as polyphenols, may also play a role in the reported beneficial effects of plant foods [3, 4]. Polyphenols are naturally occurring components in many plant-derived foods [5]. Many in vitro and animal studies have shown that polyphenols may be beneficial for cardiovascular health [6, 7, 8, 9].

Apples are a good source of various nutrients, including vitamin C and a variety of polyphenols [10]. For a long time, apples have been considered to have health-promoting effects, as illustrated by the old saying that “an apple a day keeps the doctor away”. One previous study has reported results consistent with this old saying. The study showed that higher dietary intake and/or higher blood levels of vitamin C, carotenoids, and alpha-tocopherol (as markers of fruit and vegetable intake) are associated with a reduced risk of CVD [4]. In particular, the soluble fiber content of fruits and vegetables is related to reduced blood lipid level and has a potential to prevent CVDs.

However, some studies have also reported negative effects of consuming apples, such as blood sugar fluctuations and a craving for more sugar [11]. Thus, we are interested about whether apples can truly benefit human health and reduce the risk factors for CVD.

One meta-analysis published in 2019 has focused on our topic of interest [12]. This previous study investigated the association between apple or pear intake and CVD or cardiometabolic disease. However, several differences distinguish our study from the previous meta-analysis. First, we only included randomized controlled trials (RCTs), whereas the other meta-analysis included RCTs, non-RCTs, and prospective observational studies. One reason for including only RCTs is to reduce selection bias. In addition, comparing two groups under an RCT design allows a much more straightforward interpretation. Further, we included more key indicators to better represent the potential risk of future CVD development. Therefore, through this meta-analysis involving a more accurate study method and more comprehensive health indicators [13, 14], we aimed to elucidate the effects of apple or apple polyphenols on the risk of CVD.

2. Materials and methods

2.1 Search strategy

A comprehensive systematic literature search of studies published from inception to August 4, 2020, was conducted in the PubMed (https://pubmed.ncbi.nlm.nih.gov/), Embase (https://www.embase.com/), Cochrane (https://www.cochrane.org/), and Web of Science (https://app.webofknowledge.com/author/search) databases. Our meta-analysis was performed in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines [15]. The outcomes of our study were blood pressure, total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglyceride (TG), blood glucose, and C-reactive protein (CRP) levels.

The search strategy was as follows: (hypertension [MeSH] OR blood pressure [MeSH] OR cholesterol [MeSH] OR low-density lipoprotein [MeSH] OR high-density lipoprotein [MeSH] OR triacylglycerol [MeSH] OR glucose blood level [MeSH] OR inflammation [MeSH] OR lipid [MeSH]) AND (apple [Title/Abstract] OR apple polyphenols [Title/Abstract]) AND (“randomized controlled trial [MeSH]” OR “random allocation [MeSH]” OR “[singl* OR doubl* OR trebl* OR tripl*]” AND “[blind* OR mask*]”) [16, 17].

2.2 Inclusion criteria

The eligible studies needed to meet the following criteria: (1) had an RCT design; (2) used apples or apple polyphenols as the intervention; (3) had a control group; (4) measured blood lipids (TC, HDL, LDL, and TG), systolic and diastolic blood pressure, and blood glucose or CRP levels; and (5) had an intervention time of >1 week.

2.3 Exclusion criteria

The exclusion criteria were as follows: (1) animal experiments, case reports, and review articles; and (2) duplicate reports or reports with an unclear description of outcomes.

2.4 Screening and data extraction

After searching the literature, two reviewers independently screened the search results according to the selection criteria, and uncertainties were resolved by consensus. The collected data included basic information of the studies (e.g., first author and study country), intervention time, intervention dose, sample size, demographic data (e.g., age and sex), and outcomes (e.g., blood pressure, cholesterol, and lipoproteins).

2.5 Literature quality assessment

The Jadad scale was used to assess the quality of each study [18]. A Jadad score of 3 was considered to indicate a high-quality study, whereas a score of <3 was considered to indicate a low-quality study. The strength of the evidence was assessed using the Cochrane Collaboration tool (http://meta-analysis-with-r.org (Accessed: 19 August 2021)).

2.6 Statistical analysis

A meta-analysis was conducted on the selected studies. The baseline variables and outcomes were compared between the experimental and control groups to estimate the statistical differences, whereas the standard deviation of the variation was obtained from the original study or calculated using the standard formula [19]. I2 was used to evaluate the heterogeneity among the studies. The random-effects model was chosen when I2 50%, indicating high heterogeneity among the data; otherwise, the fixed-effects model was used. Relative risks and standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated for dichotomous and continuous data using the Mantel-Haenszel and inverse variance methods, respectively. All data analyses and funnel plot analyses were performed using the Meta package (GitHub https://github.com/guido-s/meta (Accessed: 19 August 2021)) in R version 4.0.2.

3. Results

3.1 Search results

A total of 661 records were identified through the search of the four databases: 158 in Web of Science, 287 in Embase, 89 in Cochrane, and 127 in PubMed. The titles and abstracts of 469 published articles were screened after the removal of duplicates. A total of 426 studies were irrelevant to the subject, 25 studies were not RCTs, 67 studies did not meet the inclusion criteria, and 2 studies used duplicate data. Finally, 10 studies were included in our meta-analysis [20, 21, 22, 23, 24, 25, 26, 27, 28, 29] (Fig. 1, Table 1, Ref. [20, 21, 22, 23, 24, 25, 26, 27, 28, 29]).

Fig. 1.

Fig. 1.   Flow diagram of the inclusion of studies identified in the systematic review. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) template.


Table 1.   Literature characteristics.

AuthorYearAreaSample sizeDurationHealthTreatmentControlJadad
ageinterventiondoseageinterventiondose
Arrigo F.G. Cicero [20]2017Italy628 wkobese63.3 ± 7.5apple extract300 mg/d63.2 ± 11.6Placebo300 mg/d5
Ashley Eisner [21]2019America388 wkobese children10–16dried apple240 kcal/d10–16muffin240 kcal/d3
Gian Carlo Tenore [22]2019Italy548 wkCVD risk45.1 ± 10.3apple puree125 g/d48.2 ± 10.2probiotic125 g/d5
Maria Saarenhovi [23]2017Finland574 wkhealth, blood pressure high55.6 ± 7.9apple extract100 mg/d54.9 ± 6.4Placebo100 m g/d3
Mohammad Reza Vafa [24]2011Iran468 wkCVD risk41.08 ± 4.19apple300 g/d41.65 ± 3.79regular dietary300 g/d2
Sheau C. Chai [25]2012America1001 yearpostmenopausal women55.6 ± 5.0dried apple75 g/d57.5 ± 4.01dried plum75 g/d4
Stephan W. Barth [26]2012German684 wkobese23–69apple juice805.2 mg/d23–69Placebo805.2 mg/d3
Toshihiko Shoji [27]2017Japan6512 wkhealth, blood glucose high50.2 ± 1.3apple polyphenols600 mg/d51.6 ± 1.1Placebo600 mg/d4
Yoko Akazome [28]2010Japan8812 wkobese45.8 ± 8.2apple polyphenols600 mg/d45.8 ± 8.2Placebo600 mg/d3
Yoko NagasakoAkazome [29]2007Japan4812 wkobese47.8 ± 10.8apple polyphenols600 mg/d46.5 ± 10.8Placebo600 mg/d3

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3.2 Characteristics of the included studies

A total of 626 participants were included in the 10 studies. The experimental design was mostly double blind, in which the intervention group was given an oral apple polyphenol drink, apple extract, and fresh apples. Meanwhile, the control group was given the same calories of muffins, cranberries, and Lactobacillus-containing probiotics in a nonblinded experiment. The duration of the experiment was 4 weeks, 8 weeks, 12 weeks, and 1 year. Participants with one or more cardiovascular risk factors, most of whom were obese, were enrolled in the trials. The details are shown in Table 1. Fig. 2 shows that there was no publication bias in the included studies.

Fig. 2.

Fig. 2.   Funnel plot of the meta-analysis of the included studies. The logit event rate for the standardized mean difference (horizontal axis) is presented against the standard error (vertical axis). The plot shows the absence of publication bias in the included studies.


3.3 Laboratory findings

3.3.1 Effects of apples or apple polyphenols on blood lipids

Among the included studies, eight [21, 22, 23, 24, 25, 26, 27, 28] tested the TC levels in 277 participants who consumed apples or apple polyphenols and 258 control participants. The results showed no significant difference in TC levels between the two groups (SMD = 0.12, 95% CI [–0.06, 0.29], p = 0.1858, I2 = 0%, fixed-effects model). Subgroup analysis [30] was conducted for the apple and apple polyphenol groups. Compared with the control group, neither of the intervention subgroups showed significantly reduced TC levels, as shown in Fig. 3.

Fig. 3.

Fig. 3.   Forest plots of the meta-analysis on the effects of apple or apple polyphenol intake on blood lipid levels. No significant difference in total cholesterol (TC) levels was observed between the experimental and control groups.


Eight studies [20, 21, 22, 23, 24, 26, 27, 28] tested the TG levels in 277 participants who consumed apples or apple polyphenols and 258 control participants. The results showed no significant difference in the TG levels between the two groups (SMD = 0.14, 95% CI [–0.03, 0.31], p = 0.1023, I2 = 0%, fixed-effects model). Subgroup analysis was conducted for the apple and apple polyphenol groups. Compared with the control group, neither of the intervention subgroups showed significantly reduced TG levels, as shown in Fig. 4.

Fig. 4.

Fig. 4.   Forest plots of the meta-analysis on the effects of apple or apple polyphenol intake on triglyceride (TG) levels. No significant difference in TG levels was observed between the experimental and control groups.


Nine studies [20, 21, 22, 23, 24, 26, 27, 28, 29] tested the LDL-cholesterol (LDL-C) levels in 301 participants who consumed apples or apple polyphenols and 282 control participants. The results showed no significant difference in LDL-C levels between the two groups (SMD = 0.14, 95% CI [–0.02, 0.31], p = 0.1023, I2 = 3%, fixed-effects model). Subgroup analysis was conducted for the apple and apple polyphenol groups. Compared with the control group, neither of the intervention subgroups showed significantly reduced LDL-C levels, as shown in Fig. 5.

Fig. 5.

Fig. 5.   Forest plots of the meta-analysis on the effects of apple or apple polyphenol intake on low-density lipoprotein cholesterol (LDL-C) levels. No significant difference in LDL-C levels was observed between the experimental and control groups.


Ten studies [20, 21, 22, 23, 24, 25, 26, 27, 28, 29] tested the HDL-C levels in 346 participants who consumed apples or apple polyphenols and 337 control participants. Compared with the control group, the group that consumed apples or apple polyphenols showed significantly increased HDL-C levels (SMD = 0.34, 95% CI [0.01, 0.67], p = 0.0411, I2 = 77%, random-effects model). Subgroup analysis was conducted for the apple and apple polyphenol groups. Compared with the control group, the subgroup that consumed apples showed significantly increased HDL-C levels (SMD = 0.91, 95% CI [0.48, 1.34], I2 = 56%, random-effects model). However, there was no significant difference in HDL-C levels in the subgroup that consumed apple polyphenols (SMD = 0.01, 95% CI [–0.18, 0.19], I2 = 0%, fixed-effects model), as shown in Fig. 6. We conducted a sensitivity analysis of these two groups to assess the stability of the meta-analysis. When any single study was removed, the relevant pooled SMDs did not radically change. This indicates the stability of the meta-analysis, as shown in Fig. 7.

Fig. 6.

Fig. 6.   Forest plots of the meta-analysis on the effects of apple or apple polyphenol intake on high-density lipoprotein cholesterol (HDL-C) levels. Compared with the control group, participants who consumed apples or apple polyphenols showed significantly increased HDL-C levels.


Fig. 7.

Fig. 7.   Forest plots of the sensitivity analysis on the effects of apple or apple polyphenol intake on high-density lipoprotein cholesterol (HDL-C) levels. The sensitivity analysis suggested the stability of the meta-analysis.


3.3.2 Effects of apples or apple polyphenols on blood pressure

Two studies [20, 28] tested the systolic and diastolic blood pressure levels in 75 participants who consumed apples or apple polyphenols and 75 control participants. The results showed no significant difference in the systolic and diastolic blood pressure levels between the two groups (SMD = –0.4, 95% CI [–0.36, 0.28], p = 0.8212, I2 = 0%, fixed-effects model and SMD = –0.03, 95% CI [–0.35, 0.29], p = 0.8408, I2 = 0%, fixed-effects model), as shown in Figs. 8,9.

Fig. 8.

Fig. 8.   Forest plots of the meta-analysis on the effects of apple or apple polyphenol intake on systolic blood pressure. No significant difference in systolic blood pressure was observed between the experimental and control groups.


Fig. 9.

Fig. 9.   Forest plots of the meta-analysis on the effects of apple or apple polyphenol intake on diastolic blood pressure. No significant difference in diastolic blood pressure was observed between the experimental and control groups.


3.3.3 Effects of apples or apple polyphenols on blood glucose or CRP

Four studies [20, 21, 22, 28] tested the blood glucose levels in 127 participants who consumed apples or apple polyphenols and 115 control participants. The results showed no significant difference in the blood glucose levels between the two groups (SMD = –0.14, 95% CI [–0.40, –0.12], p = 0.2837, I2 = 37%, fixed-effects model), as shown in Fig. 10.

Fig. 10.

Fig. 10.   Forest plots of the meta-analysis on the effects of apple or apple polyphenol intake on blood glucose levels. No significant difference in blood glucose levels was observed between the experimental and control groups.


Four studies [21, 23, 25, 26] tested the CRP levels in 165 participants who consumed apples or apple polyphenols and 155 control participants. Compared with the control group, the group that consumed apples or apple polyphenols showed significantly decreased CRP levels (SMD = –0.43, 95% CI [–0.65, –0.20], p = 0.0002, I2 = 18%, fixed-effects model), as shown in Fig. 11.

Fig. 11.

Fig. 11.   Forest plots of the meta-analysis on the effects of apple or apple polyphenol intake on C-reactive protein (CRP) levels. Compared with the control group, the group that consumed apples or apple polyphenols showed significantly decreased CRP levels.


4. Discussion

In 2016, an estimated 17.9 million people died of CVD, accounting for 31% of all deaths worldwide, according to the World Health Organization. In our study, we found that apple or apple polyphenol consumption can increase HDL-C levels and decrease CRP levels. This may be the reason why apples are beneficial to cardiovascular health and can potentially prevent future CVD development [3, 4].

The results of this study are consistent with previous evidence suggesting that apples fulfill the expectations from the famous saying about keeping doctors away [3, 31]. Researchers from Florida State University reported at the 2011 Experimental Biology Conference in Washington that elderly women who consumed apples daily had reduced LDL-C levels (by an average of 23%) and increased HDL-C levels (by 4%) within 6 months, illustrating those apples are indeed a “magic fruit”. Nagasako-Akazome et al. [29] targeted healthy men and women with slightly elevated serum cholesterol levels in their study. After the administration of food tablets containing apple polyphenols for 4 weeks, the data showed that the polyphenols from apples actively inhibited the absorption and accelerated the excretion of cholesterol, resulting in a decreased serum cholesterol level. The underlying mechanism is that apple polyphenols combine with cholesterol and/or bile acids, thereby enhancing the excretion of these compounds in feces; thus, polyphenols can inhibit the enterohepatic circulation of cholesterol and bile acids. Moreover, in another study that was conducted on 40 mildly hypercholesterolemic volunteers who consumed two apples per day for 8 weeks, a significant reduction was observed in serum TC, LDL-C, and plasma intercellular adhesion molecule-1 levels, with no detrimental effect on HDL-C levels, compared with sugar-matched controls [10].

The results also showed that the consumption of apple or apple polyphenols had no significant effect on the serum levels of TC and LDL-C and on blood pressure, in agreement with the results of other studies. In an early study, 28 participants with normal cholesterol levels were recruited. They were separated into two groups: one group consumed 375 mL of unsupplemented apple juice per day and the other group consumed 340 g of cored whole apple per day for 6 weeks. Thereafter, the participants were crossed over to the alternate intervention for another 6 weeks. After 12 weeks of observation, no significant difference was observed between the two groups in the serum levels of TC, LDL-C, and apolipoprotein B, whereas a low and insignificant increase was observed in fasting TG levels [32]. In another study, 15 individuals with an average age of 67–75 years consumed 2 g/kg body weight of apple daily for 1 month and showed no significant difference in the levels of serum TG, TC, LDL, HDL, and very LDL [33].

The participants included in our analysis and in other studies who showed no significant differences after the intervention were considered healthy individuals. Although some experimental participants were slightly overweight and had one or several risk factors, their physical condition was generally healthy. Therefore, daily intake of apples with low polyphenol content will not have a positive and significant effect on blood lipid levels, as in individuals with symptoms. Nagasako-Akazome et al. [29] reported that daily intake of 600 mg apple polyphenol extract caused a significant decrease in serum TC and LDL-C levels. This amount of apple polyphenol intake was much greater than the dose used in the other studies included in the meta-analysis. Therefore, the insufficient amount could be a possible explanation for the observed insignificances.

Moreover, we observed some insignificant increases in serum TC, TG, and LDL-C levels. The mechanisms leading to increased serum TG levels may include increased intake of fructose from the consumption of apples [34]. An increase in dietary fructose intake will increase the liver lipogenesis activity of enzymes, leading to increased TG levels.

Although we obtained some promising results from our analysis, it is important note that the included studies were performed over a relatively short period (most of the studies lasted approximately 4–8 weeks). Thus, no conclusions on the long-term effects of polyphenols can be drawn. After a careful screening, only 10 articles were included in the analysis. As this amount of literature is not very representative, our results cannot be used to generalize the effects of apple or apple polyphenols on the prevention of CVDs. The diversity of participants was also a limitation. In the studies included in our analysis, more than half of the participants were overweight. More studies including participants with normal weight or even underweight are needed to obtain comprehensive information about the effects of apple or apple polyphenols.

5. Conclusions

In conclusion, although apple or apple polyphenol consumption had no significant effect on the serum levels of TC and LDL-C and on blood pressure, we still found that apple or apple polyphenol intake can effectively increase HDL-C levels, reduce CRP levels, and potentially reduce the risk of CVD. However, because of the small number of included studies, small sample sizes, different conditions of the included participants, and short intervention periods, our findings have certain limitations. To obtain more meaningful results, future studies should consider expanding the scope of participants to include all kinds of people with different physical signs.

Author contributions

XZ and GX conceptualized the study. WJ involved in formal analysis. YG designed methodology. XH and LG collected the data. XZ and GX wrote the original draft. WJ, YG, XH and LG wrote, reviewed, and edited the manuscript. Finally, all authors read and approved this manuscript for publication.

Ethics approval and consent to participate

Not applicable.

Acknowledgment

Not applicable.

Funding

This research received no external funding.

Conflict of interest

The authors declare no conflict of interest.

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