Food and Nutrition Sciences
Vol.5 No.13(2014), Article ID:47722,13 pages DOI:10.4236/fns.2014.513134

Apple as a Source of Dietary Phytonutrients: Bioavailability and Evidence of Protective Effects against Human Cardiovascular Disease

Gianna Ferretti1*, Imma Turco1, Tiziana Bacchetti2

1Dipartimento di Scienze Cliniche Sperimentali e Odontostomatologiche, Università Politecnica delle Marche, Ancona, Italia

2Dipartimento di Scienze Della Vita e dell’Ambiente, Università Politecnica delle Marche, Ancona, Italia

Email: *g.ferretti@univpm.it

Copyright © 2014 by authors and Scientific Research Publishing Inc.

This work is licensed under the Creative Commons Attribution International License (CC BY).

http://creativecommons.org/licenses/by/4.0/

Received 19 April 2014; revised 20 May 2014; accepted 4 June 2014

ABSTRACT

The dietary consumption of fruit and vegetable is associated with a lower incidence of degenerative diseases such as cardiovascular disease. Most recent interest has focused on the bioactive phenolic compounds in vegetable products. All varieties of apple contain several antioxidants and polyphenols that possess many biological activities, such as antioxidant and anti-inflammation properties. The review describes the nutritional properties of apples and their derivatives, with a particular attention to polyphenol compounds. Moreover, the health benefits of apples and the potential molecular mechanisms against cardiovascular disease are reviewed.

Keywords:Antioxidants, Apples, Cardiovascular Disease, Phytocompounds, Polyphenols

1. Introduction

Several studies have demonstrated that fruits and vegetables exert a protective effect against the development of human diseases such as cardiovascular disease, diabetes and cancer [1] -[4] . It has been hypothesized that the protective role could be due to nutrients contained in the vegetables such as fiber, vitamins and phytochemicals. Among phytochemicals, the protective role of phenolics has been mainly investigated. Phenolics are secondary plant metabolites characterized by having at least one aromatic ring with one or more hydroxyl groups attached. The nature and the distribution of phenolics differ by plant tissue, with many of the phenolics synthesized from carbohydrates via the shikimate and phenyl propanoid pathways. Phenolics range from simple, low molecular weight, single-aromatic ring compounds to the large complex tannins. Polyphenols generally occur as glycosylated derivatives in plants, although conjugation with inorganic acid and malonylation is also known [5] [6] .

Apples are among the most widely consumed fruits in various countries. They are widely consumed fresh or in processed forms, such as juices and dried apple. Apples contain several nutrient as well as non-nutrient components, including dietary fiber, minerals, and vitamins (Table 1). Moreover, apple is one of the main natural sources of phytochemicals most of which express relevant antioxidant capacities in vitro [7] -[9] . The biological activities of apple polyphenols have often been evaluated in vitro on cultured cells and in animal models [7] [10] [11] . Previous studies have also investigated the effect of apples derivatives. Among these, apple pomace, a waste material from apple juice processing, which contains significant amounts of dietary fiber and phytochemicals has been studied [12] [13] . However, it has to be stressed that it is not always clear whether the effects in animals can be extrapolated to humans. Furthermore, studies in cell culture have been conducted before it is known that phytochemicals are processed in vivo, how they are absorbed and metabolized in the body. For

Table 1 . Average nutrient content in apple (per 100 g fresh weight) (Jensen et al. 2009).

a. in red apples.

example, some phytochemicals are fermented by colonic bacteria and the original phytochemical may not even be detectable in the blood [14] .

This review focuses on the nutrient and phytochemical contents of apples. An overview on the bioavailability and metabolism of the most abundant apple phytochemicals after consumption is also presented, and the currently hypothesized health benefits related to apple consumption in humans are reviewed, with a particular attention given to recent evidence on the impact of apple on cardiovascular health and the biological effects related to the protective effect of this fruit.

2. Apples Nutritional Properties and Phytochemicals

The chemical composition and the nutritional properties of different cultivar of apple and their derivatives (juice, dried apple) have been previously studied [15] [16] . According to its nutrient profile (Table 1), apple represents a healthy food choice.

2.1. Sugars

Ninety-percent of the energy from apples is derived from simple carbohydrates, mainly sugars, of which fructose is the dominant form. Apple fructose and sucrose contents are lower than in most other fruits.

The fibre content of apple is approx. 3 g/100 g fresh weight (FW) and consists mainly of soluble fibres (pectin) (Table 1). Pectin is a complex polysaccharide, and apple pectin exhibits a high degree of esterification and a particularly high content of branched side chains [17] . Pectin exerts different physiological roles. It exerts prebiotic effects [18] and is fermented by the microflora in the large intestine resulting in the formation of short chain fatty acids (SCFA) which are absorbed and metabolised in the colonic mucosa, liver, or peripheral tissues. It has been established a relationship between the consumption of pectins and maintenance of normal blood cholesterol concentrations and a reduction of post-prandial glycaemic responses [19] .

2.2. Micronutrients

Apple also contains several nutrient as well as non-nutrient components, including, minerals, and vitamins. Apples are rich in vitamins C and E, some pro-vitamin A carotenes, lutein, folic acid, potassium and magnesium (Table 1).

2.3. Phytochemicals

Some of the most well studied polyphenol compounds in apples include flavonoids such as quercetin-3-galactoside, quercetin-3-glucoside, quercetin-3-rhamnoside [7] [15] . Lister et al. [20] reported quercetin glycoside concentrations of 400 - 700 mg/100 g and 250 - 550 mg/100 g in Granny Smith and Splendour apple peels, respectively, with quercetin 3-galactoside (hyperin), quercetin 3-arabinofuranoside (avicularin), quercetin 3- rhamnoside (quercetin), and quercetin 3-xyloside (reynoutrin) being the four most common. Apples contain also flavanols ([+]catechin [−]epicatechin). Other phytochemicals are antocyanins (cyanidin-3-galactoside), coumaric acid, chlorogenic acid, gallic acid, and certain dihydrochalcones only found in apples (phloridzin and phloretin) [21] . Schieber et al., [22] have demonstrated the presence of isorhamnetin glycosides in extracts of “Brettacher” apples that are used both as a dessert fruit and for juice. The flavanols of apples are very similar to those present in cocoa and dark chocolate, and apples represent potential sources of extractable flavanols for inclusion in functional foods. The apple contains also condensed tannins. The apple condensed tannins (ACT) are contained in unripe apples at a ten times higher level than in the ripe ones [23] . Condensed tannins are called proanthocyanidins (PA). PA differ from all other natural polyphenols by their polymeric nature. They are made of flavan-3-ol units and their average degree of polymerization generally varies between 3 and 11 [24] . Polymerization degree may reach values as high as 17 as was shown in an apple cider extract by Guyot et al. [25] . We consume small amounts of these compounds in daily life from fresh fruits such as apple and the processed foods made from these fruits.

Previous studies have also evaluated the concentration of phytochemicals between the apple peels and the apple flesh. Apple peels contain from two to six times (depending on the variety) more phenolic compounds than in the flesh, and two to three times more flavonoids in the peels when compared to the flesh. The antioxidant activity of apple peels is much greater, ranging from two to six times greater in the peels when compared to the flesh, depending on the variety of the apple [7] -[9] . Quercetin conjugates are found exclusively in the peel of the apples. Chlorogenic acid tends to be higher in the flesh than in the peel. In agreement with the polyphenol composition, apples with the peels are better able to inhibit cancer cell proliferation when compared to apples without the peels [26] .

3. Bioavailability of Apple Phytochemicals in Humans

Bioavailability is defined as the proportion of a phytochemical that is digested, absorbed, and utilized in normal metabolism; however, measurement of bioavailability relies heavily upon estimates of amounts of antioxidant absorbed. Positive health effects of apple-derived polyphenols in vivo depend on their absorption, metabolism, distribution, and elimination from the body after consumption. Prerequisites for these compounds to have any in vivo effects are that they must be absorbed from the gastrointestinal tract after food consumption and subsequently reach sufficiently high plasma concentrations in the systemic circulation to induce biological activity. Bioavailability of polyphenols may be influenced by food matrix and dose ingested. A major part of the polyphenols ingested (75% - 99%) is not found in urine. This implies they have either not been absorbed through the gut barrier, absorbed and excreted in the bile or metabolized by the colonic microflora or our own tissues. Only very rare measurements of the intestinal absorption of polyphenols in humans are available [14] [27] [28] . Large uncertainties remain due to the lack of comprehensive data on the content of some of the main polyphenol classes in food. The maximum concentration in plasma rarely exceeds 1 microM after the consumption of 10 - 100 mg of a single phenolic compound. However, the total plasma phenol concentration is probably higher due to the presence of metabolites formed in the body’s tissues or by the colonic microflora. The bioavailability of some apple phytonutrients has been recently investigated in human studies and the results are summarized.

Dihydrochalcones. Phloretin (Phl) has been found exclusively in apples and in apple-derived products where is present as free and its glucosidic form, phloridzin (phloretin 2’-O-glucose). The bioavailability of dihydrochalcones following the consumption of apples and apple cider has been investigated in ileostomists and healthy subjects [29] [30] . After ingestion, the principal component in apples and cider, phloretin glucosides undergo cleavage in the small intestine with the released phloretin being subject to glucuronidation before appearing rapidly in the circulatory system as plorethin-2-O-glucuronide with a Tmax lower than 1 h. The short duration of the Tmax values and the similar Cmax of the glucuronide in healthy subjects and in ileostomist subjects after apple cider intake are indicative of absorption in the prossimal gastrointestinal tract. Glucuronide derivative has been detected in ileal fluid, urine, and plasma samples in addition to minor amounts of Phl conjugates (glucuronides and sulfates) and unconjugated Phl in the ileal samples [29] [30] .

Epicatechin. The bioavailability of the flavanol epicatechin has been studied using an apple extract (apple drink) and an apple puree containing different amounts of epicatechin (70 mg and 140 mg) [31] . The results of the randomized, placebo-controlled, crossover trial demonstrated that maximum plasma concentration, absorption and urinary excretion were all significantly higher after ingestion of both epicatechin drinks compared with apple puree (p < 0.05). Epicatechin bioavailability was >2-fold higher after ingestion of the 140 mg epicatechin drink compared to the 70 mg epicatechin drink (p < 0.05). The authors concluded that oral bioavailability of apple epicatechin increased at higher doses, but was reduced by whole apple matrix when compared with a epicatechin-rich apple extract incorporated in water-based drink [31] .

Quercetin. As far as it concerns the bioavailability of apple quercetin, previous studies have demonstrated that is lower when compared with onions [32] . DuPont et al. [33] have also determined the uptake and excretion of low doses of polyphenols in six subjects who each consumed 1.1 L of an alcoholic cider beverage. No quercetin was found in urine or plasma, but 3’-methyl quercetin was detected in plasma suggesting that low doses of quercetin are extensively methylated in humans [28] [33] .

Condensed tannin bioavailability. Very little is known about the metabolic fate and bioavailability of tannins. Proanthocyanidins (PA) absorption depends on their degree of polymerization [34] . In some in vitro experiments, only PA dimers and trimers, but not polymers with an average polymerization degree of 7, were absorbed through an intestinal epithelium cell monolayer [35] . Déprez et al. [36] have demonstrated that in vitro PA are catabolized by human colonic microflora into low-molecular-weight phenolic acids.

Other apple polyphenols. Two human intervention studies have investigated the bioavailability of other apple polyphenols in healthy men after ingestion of apples from different farming systems. The short-term intervention study included six men who consumed either organically or conventionally produced apples (randomized cross-over study). After intake of 1 kg apples, phloretin and coumaric acid plasma concentrations increased significantly (p < 0.0001) in both intervention groups, without differences between the two farming systems. In the long-term intervention study, 43 healthy volunteers consumed organically or conventionally produced apples (500 g/day; 4 weeks) or no apples in a double-blind, randomized intervention study. In the study, 24 h after the last dosing regime, the apple intake did not result in increasing polyphenol concentrations in plasma and urine compared to the control group suggesting no accumulation of apple polyphenols or degradation products in humans [37] .

5. Conclusions

In vitro apple polyphenols have been identified as potent radical scavenger, antioxidant and anti-inflammatory molecules. The effect of different varieties of apple has been recently investigated in human epidemiologic and

Table 4 . Potential disease-preventive mechanisms of apple and their active constituents as identified in human dietary studies.

interventional studies. The results demonstrate that the consumption of the fresh and dried apple exerts a beneficial effect to human health. Different molecular mechanisms, as summarized in Table 4, can be suggested to explain the protective effect exerted by apple components.

The beneficial effects of whole apples on plasma lipid levels are probably related to synergistic interactions between apple components. Contrasting results have been reported in obese and hypercholesterolemic patients. Additional human studies are needed to confirm the hypothesized antioxidant, antinflammatory, and vascular protective effects of apples and derivatives in normal and pathological conditions.

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Abbreviations

ACT, apple condensed tannins;

AJ, apple juice;

CRP, C-reactive protein;

CVD, cardiovascular disease;

FMD, flow-mediated dilatation;

FW, fresh weight;

GPX, glutathione peroxidase;

NO, nitric oxide;

RXNO, nitrosylated species;

Phl, phloretin;

LDL, low-density lipoprotein;

LDL-C, LDL-cholesterol;

PA, proanthocyanidins;

ROS, reactive oxygen species;

SCFA, short chain fatty acids;

SOD, superoxide dismutase;

TAG, triacylglicerol;

TBARS, thiobarbituric acid-reactive substances;

NOTES

*Corresponding author.