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.

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.

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.

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.

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This research received no external funding.

The authors declare no conflict of interest.