Apple and Apple Phytochemicals,how strange a common fruit so magic use?

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   Apple and Apple Basic Data:
 

 Botanical: Pyrus malus
 Synonyms:Wild Apple. Malus communis.
 Parts Used:The fruit and the bark.
 Habitat:Temperate regions of the Northern Hemisphere.

  History:

 The Apple is a fruit of the temperate zones and only reaches perfection in their cooler regions. It is a fruit of long descent and in the Swiss lake-dwellings small apples have been found, completely charred but still showing the seed-valves and the grain of the flesh. It exists in its wild state in most countries of Europe and also in the region of the Caucasus: in Norway, it is found in the lowlands as far north as Drontheim.

 The Crab-tree or Wild Apple (Pyrus malus), is native to Britain and is the wild ancestor of all the cultivated varieties of apple trees. It was the stock on which were grafted choice varieties when brought from Europe, mostly from France. Apples of some sort were abundant before the Norman Conquest and were probably introduced into Britain by the Romans. Twenty-two varieties were mentioned by Pliny: there are now about 2,000 kinds cultivated. In the Old Saxon manuscripts there are numerous mentions of apples and cider. Bartholomeus Anglicus, whose Encyclopedia was one of the earliest printed books containing botanical information (being printed at Cologne about 1470), gives a chapter on the Apple. He says:

 'Malus the Appyll tree is a tree yt bereth apples and is a grete tree in itself. . . it is more short than other trees of the wood wyth knottes and rinelyd Rynde. And makyth shadowe wythe thicke bowes and branches: and fayr with dyurs blossomes, and floures of swetnesse and Iykynge: with goode fruyte and noble. And is gracious in syght and in taste and vertuous in medecyne . . . some beryth sourysh fruyte and harde, and some ryght soure and some ryght swete, with a good savoure and mery.'


  Apple Constituents:

 Various analyses show that the Apple contains from 80 to 85 per cent. of water, about 5 per cent. of proteid or nitrogenous material, from 10 to 15 per cent. of carbonaceous matter, including starch and sugar, from 1 to 1.5 per cent. of acids and salts. The sugar content of a fresh apple varies from 6 to 10 per cent., according to the variety. In spite of the large proportion of water, the fresh Apple is rich in vitamins, and is classed among the most valuable of the anti-scorbutic fruits for relieving scurvy. All apples contain a varying amount of the organic acids, malic acid and gallic acid, and an abundance of salts of both potash and soda, as well as salts of lime, magnesium, and iron.

 It has been calculated that in 100 grams of dried apples, there are contained 1.7 milligrams of iron in sweet varieties and 2.1 milligrams in sour varieties. It has also been proved by analysis that the Apple contains a larger quantity of phosphates than any other vegetable or fruit.
 The valuable acids and salt of the Apple exist to a special degree in and just below the skin, so that, to get the full value of an apple, it should be eaten unpeeled.
 The bark of the Apple-tree which is bitter, especially the root-bark, contains a principle called Phloridzin, and a yellow colouring matter, Quercetin, both extracted by boiling water. The seeds give Amygdaline and an edible oil.
 Apple oil is Amyl Valerate or Amylvaleric Ester. An alcoholic solution has been used as a flavouring liquid, called Apple Essence.
 Fresh apple-juice is employed for the N.F. Ferrated Extract of Apples.

 

 Apple and Apple Basic Data:
 Apple phytochemicals:
 Bioavailability of phytochemicals:
 Effects of variety and ripening on apple phytochemicals:
 Health benefits of apples: epidemiological evidence:
 Frequently Asked Questions:
 Apples:Witches Brew
 From Findings of Apple Procyanidin B-2:
 Properties and effects of Polyphenol from Apple:
 Processing Method:Concentration of phenolics extracted from apples:
 Apple Polyphenol and Its Application to Tooth coating composition:
 Phloridzin-rich phenolic fraction and use thereof as a cosmetic, dietary or nutraceutical agent:
 Research and Findings:Apple Polyphenol
 Apple Polyphenol:toxicology and safety.
 How search engine think about Apple:
 Research update of Apple and Apple Phytochemicals:


   Apple phytochemicals:

 Apples contain a large concentration of flavonoids, as well as a variety of other phytochemicals, and the concentration of these phytochemicals may depend on many factors, such as cultivar of the apple, harvest and storage of the apples, and processing of the apples. The concentration of phytochemicals also varies greatly between the apple peels and the apple flesh.

 Some of the most well studied antioxidant compounds in apples include quercetin-3-galactoside, quercetin-3-glucoside, quercetin-3-rhamnoside, catechin, epicatechin, procyanidin, cyanidin-3-galactoside, coumaric acid, chlorogenic acid, gallic acid, and phloridzin (Figure 2). Recently researchers have examined the average concentrations of the major phenolic compounds in six cultivars of apples. They found that the average phenolic concentrations among the six cultivars were: quercetin glycosides, 13.2 mg/100 g fruit; vitamin C, 12.8 mg/100 g fruit; procyanidin B, 9.35 mg/100 g fruit; chlorogenic acid, 9.02 mg/100 g fruit; epicatechin, 8.65 mg/100 g fruit; and phloretin glycosides, 5.59 mg/100 g fruit.

 The compounds most commonly found in apple peels consist of the procyanidins, catechin, epicatechin, chlorogenic acid, phloridzin, and the quercetin conjugates. In the apple flesh, there is some catechin, procyanidin, epicatechin, and phloridzin, but these compounds are found in much lower concentrations than in the peels. Quercetin conjugates are found exclusively in the peel of the apples. Chlorogenic acid tends to be higher in the flesh than in the peel.

 Because the apple peels contain more antioxidant compounds, especially quercetin, apple peels may have higher antioxidant activity and higher bioactivity than the apple flesh. Research showed that apples without the peels had less antioxidant activity than apples with the peels. Apples with the peels were also better able to inhibit cancer cell proliferation when compared to apples without the peels. More recent work has shown that apple peels contain anywhere 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 these peels was also much greater, ranging from two to six times greater in the peels when compared to the flesh, depending on the variety of the apple. This work is supported by Leontowicz et al who found that rats consuming apple peels showed greater inhibition of lipid peroxidation and greater plasma antioxidant capacity when compared to rats fed apple flesh.


 Many of these phytochemicals from apples have been widely studied, and many potential health benefits have been attributed to these specific phytochemicals. The procyanidins, epicatechin and catechin, have strong antioxidant activity and have been found to inhibit low density lipoprotein (LDL) oxidation in vitro. In mice, catechin inhibits intestinal tumor formation and delays tumors onset. Sawa et al. (1999) found that chlorogenic acid has very high alkyl peroxyl radical (ROO?) scavenging activity. Compared to about 18 other antioxidant compounds (including quercetin, gallic acid, alpha-tocopherol), chlorogenic was second only to rutin. Since ROO? may enhance tumor promotion and carcinogenesis, chlorogenic acid may add to the protective effect of apples against cancer. Chlorogenic acid has been found to inhibit 8-dehydroxy-deoxyguanosine formation in cellular DNA in a rat model following treatment with 4-nitroquinoline-1-oxide.

 Quercetin is also a strong antioxidant, and is thought to have potential protective effects against both cancer and heart disease. Briefly, quercetin has been found to down regulate expression of mutant p53 in breast cancer cells, arrest human leukemic T-cells in G1, inhibit tyrosine kinase, and inhibit heat shock proteins. Quercetin has protected Caco-2 cells from lipid peroxidation induced by hydrogen peroxide and Fe2+. In mice liver treated with ethanol, quercetin decreased lipid oxidation and increased glutathione, protecting the liver from oxidative damage. Recently, it has been found that high doses of quercetin inhibit cell proliferation in colon carcinoma cell lines and in mammary adenocarcinoma cell lines, but at low doses quercetin increased cell proliferation (20% in colon cancer cells and 100% in breast cancer cells). However, low doses of quercetin (10 uM) inhibited cell proliferation in Mol-4 Human Leukemia cells and also induced apoptosis. Quercetin inhibited intestinal tumor growth in mice, but not in rats. Low levels of quercetin inhibited platelet aggregation, calcium mobilization, and tyrosine protein phosphorylation in platelets. Modulation of platelet activity may help prevent cardiovascular disease.

 Both animal and cell culture studies show that there is an association between the polyphenolic compounds found within apples and a wide variety of effects that may help prevent chronic disease. This supports the hypothesis that it is the phytochemicals found in fruits, especially apples, that impart healthy benefits. More research is still needed to clarify the effects of these compounds in vivo. In order to examine the effects of these compounds in vivo, it is necessary to understand the bioavailability of the specific compounds, and the bioavailability of these compounds within the fruit matrix.


   Bioavailability of phytochemicals:
 

 As the link between diet and chronic disease grows stronger, many are working to understand how phytochemicals may provide health benefits. An important question to be asked is: Are these phytochemicals bioavailable? Concentrations and bioavailability of phytochemicals are important issues to evaluate when characterizing the effects of dietary phytochemicals on human health. To this date, little literature exists that addresses the bioavailability of phytochemicals from whole foods, including the apple. One of the few studies addressing bioavailability from apples or apple products looks at the bioavailability of polyphenolic compounds from alcoholic apple cider in humans. After drinking 1.1 liters of apple cider, no quercetin was found in the volunteers' plasma. Instead, low levels of 3'-methyl quercetin and 4'-methyl quercetin were seen within 60 minutes following consumption of the cider. Caffeic acid was rapidly absorbed, but within 90 minutes the caffeic levels in the plasma were undetectable. Catechin, epicatechin, and phlorizin were not seen in the plasma, possibly because the concentration in the cider was too low. Hippuric acid and phloretin were both increased in the subjects' urine following the consumption of the cider, but there was no evidence of quercetin, catechin, or epicatechin in the urine.

 In another study involving human subjects, quercetin bioavailability from apples was only 30% of the bioavailability of quercetin from onions. In this study, quercetin levels reached a peak after 2.5 hours in the plasma, however the compounds were hydrolyzed prior to analysis, so the extent of quercetin conjugation in the plasma is unknown. The bioavailability differences between apples and onions most likely are from the differences in quercetin conjugates in the different foods. Onions contain more quercetin aglycone and more quercetin glucosides, whereas apples tend to contain more quercetin monoglycosides and quercetin rutinoside, which may be less bioavailable. Our lab has examined the bioavailability of both quercetin and quercetin-3-glucoside from apple peel extracts and onion extracts in Caco-2 cells. Apple peel extracts contained no free quercetin, and no quercetin accumulation was seen in the Caco-2 cells following incubation with apple peel extract. Low amounts of quercetin-3-glucoside were absorbed by the cells (4%). However, onions contain some free quercetin and greater amounts of quercetin glucosides, and the absorption of quercetin into the Caco-2 cells from onion extracts was much greater than from apple extracts.

 The above results can be explained by recent research examining quercetin and quercetin glycoside bioavailability. In a study by Walle et al. , it was found that, in the ileostomy fluid, quercetin primarily existed as the aglycone form. The group hypothesized that beta-glucosidases hydrolyzed quercetin glucosides to quercetin, which could be then passively transported. In support of this theory, Day et al. determined that quercetin glycosides were mainly deglycosylated by lactase phlorizin hydrolase before the aglycone then passed into the cell. Some intact glycoside transport by SGLT1 occurred and the glucosides were deglycosylated within the cell by cytosolic beta-glucosidase. Quercetin-3-glucoside appeared to utilize only the lactase phlorizin hydrolase pathway, not the SLGT1 transporter, but quercetin-4-glucoside used both pathways. Apples contain some quercetin-3-glucoside that, following hydrolysis by LPH, would be available for uptake by intestinal cells. However, apples also contain other conjugates such as quercetin rhamnosides, quercetin xylosides, and quercetin galactosides that are not easily hydrolyzed by lactase phlorizin hydrolase, and most likely are not readily absorbed by small intestinal cells. In comparison, the quercetin in onions is almost all in the form of quercetin glucosides and free quercetin, making it more bioavailable to small intestinal cells.

 Some bacterial degradation of quercetin conjugates most likely occurs in the human intestinal tract. Enterococcus casseliflavis and Eubacterium ramulus, microorganisms isolated from human feces, were both found to degrade quercetin-3-glucoside as a carbon and energy source. Enterococcus casseliflavis utilized only the sugar moiety of the glucoside, whereas Eubacterium ramulus was also capable of degrading the aromatic ring system with phloroglucinol produced as an intermediate.

 Phloridzin, the glucoside conjugate of phloretin, is the major dihydrochalcone found in apples. Similarly to quercetin glucosides, phloridzin is thought to be hydrolyzed by lactase phloridzin hydrolase, and phloretin aglycone is taken up by the intestinal cells. When rats were fed phloridzin and phloretin, their plasma contained glucuronidated and sulfated phloretin but no phloridzin. This supports the theory that phloridzin is hydrolyzed prior to uptake and further glucuronidation by intestinal epithelial cells. Phloridzin is known to be a potent SGLT1 inhibitor, but recently it has been discovered that phloridzin is also transported by SGLT1. However, phloridzin, as well as other flavonoid glucosides such as quercetin glucoside, is also effluxed by the multi-drug resistance protein (MRP1).

 In human ileostomy subjects, chlorogenic acid absorption was approximately 33%, and only traces of chlorogenic acid was found in the urine. The majority of chlorogenic acid will reach the large intestine and may be metabolized by the gut microflora. Gonthier et al (2003) found that rats fed chlorogenic acid excrete very little chlorogenic acid in their urine, but instead they excrete mainly microbial produced metabolites of chlorogenic acid, such as hippuric acid and m-coumaric acid. A more recent study by Olthof et al (2003) involving human subjects showed that half of the ingested chlorogenic acid was converted to hippuric acid in the colon, most likely by microbial metabolism.

 Catechin and epicatechin are both absorbed by small intestinal epithelial cells. In contrast to quercetin, epicatechin was not glucuronidated by human liver microsomes, nor was it glucuronidated by human small intestinal or large intestinal tissue. Both liver and intestinal tissues contain UDP-glucuronosyltransferases (UGT) that are involved in the glucuronidation of various other flavonoids. Epicatechin was found to be sulfated by the human liver and intestinal cytosols, indicating that sulfation is the major metabolic pathway for epicatechin metabolism.

 The mechanisms concerning the bioavailability of specific apple phytochemicals are becoming clearer as bioavailability research increases. In general, many flavonoid aglycones tend to pass through the intestinal epithelial cells where they are further conjugated. The flavonoid glycosides may be absorbed in small amounts, but most absorption seems to occur following hydrolysis by intestinal hydrolases such as lactase phloridzin hydrolase. Upon absorption these compounds are also conjugated. More research is still needed to understand the bioavailability of compounds from whole foods. The effects of the food matrix, interactions between compounds, digestion and processing on bioavailability of apple phytochemicals are still unknown.

  Varietal differences:

 

 

   Effects of variety and ripening on apple phytochemicals:

  Varietal differences:

 Researchers have found distinct differences in total phenolic and total flavonoid content between different apple varieties. Of four common varieties used for applesauce (Rome Beauty, Idared, Cortland, and Golden Delicious), Rome Beauty had the highest phenolic content while Cortland apples had the lowest. Rome Beauty apples also had the highest flavonoid content while Cortland apples had the lowest. However, Idared contained much higher anthocyanins than any of the other varieties. Anthocyanins are the antioxidant compounds in the fruits that may give fruit a red or blue color. Out of 10 varieties commonly consumed in the US, apples of China had the highest total phenolic and total flavonoid compounds. Red Delicious apples were also quite high, and the apples containing the lowest amounts of phenolics and flavonoids were the Empire apples and the NY647 apple. Antioxidant activity of apples also differs between different varieties, and was positively associated with the level of total phenolic content. The apple varieties with the higher phenolics tended to have higher antioxidant activity.

 Researchers have found similar variations in phytochemical content between different cultivars of apples. Van der Sluis et al (2001) found that Jonagold apples contained the highest concentration of quercetin glycosides, catechins, and chlorogenic acid when compared to Golden Delicious, Cox's Orange, and Elstar apples. Golden Delicious had the second highest concentration, while Cox's Orange and Elstar had the lowest concentrations. Escarpa and Gonzalez (1998) found that Golden Delicious had the lowest concentration of flavonoids when compared to Reinata, Red Delicious, and Granny Smith apples. Reinata had the highest level of flavonoids, followed by Granny Smith and Red Delicious varieties. Another group looked solely at procyanidin content of four varieties of apples and found that Granny Smith and Red Delicious had the highest procyanidins while McIntosh and Golden Delicious had the lowest.

  Growth conditions:

 Besides variety of apple, factors such as development and ripening of the fruits may impact phytochemical profiles in apples. Quercetin glycosides, phloridzin, catechins, and chlorogenic acid concentrations in Jonagold and Elstar apples were highest early in the season, and decreased to a steady level during maturation and ripening. Anthocyanins in Elstar and Jonagold apples started high and decreased in mid-season, but rose rapidly just prior to maturation. Interestingly, this increase in anthocyanin content occurred only in fruits grown in the outer part of the canopy, and not in those grown in the inner part of the canopy. The amounts of quercetin glycosides in both Jonagold and Elstar were also greater in fruit grown in the outer canopy. Awad (2000) also found that sun exposed fruits (both Jonagold and Elstar) had greater levels of anthocyanins and quercetin glycosides when compared to the shaded fruits, giving more evidence that exposure to sunlight affects these two compounds production. In general, it can be concluded that improving light exposure for apples may help increase the production of certain phytochemicals. There was no sunlight effect on phloridzin, catechin, and chlorogenic acid.

  Plant nutrition:

 The effect of different nutrients on flavonoids and chlorogenic acid in apples has also been examined. Awad (2002) found that nitrogen fertilization was associated with decreases in anthocyanins, catechins and total flavonoids, and also with decreased percentage of blush in the fruit peels. In Elstar apples, calcium fertilization was associated with an increase in anthocyanins and total flavonoids. They also examined the effects of applications of different chemicals that may enhance ripening on the formation of different phytochemicals. Ethephon increased anthocyanin production, but did not increase chlorogenic acid or any of the other phytochemicals studied. Gibberellins and (s)-trans-2-amino-4-(2-aminoethoxy)-3-butenoic acid hydrochloride (ABG-3168) both decreased anthocyanin production, but did not have an effect on other compounds studied. The application of other chemicals, such as alar, cycocel, seniphos, shikimic acid, plantacur-E and galactose did not have an effect on any of the phytochemicals examined.

  Effects of storage and processing on apple phytochemicals storage:

 Apple phytochemical content is not greatly affected by storage. Quercetin glycosides, phloridzin, and anthocyanin content of Jonagold, Golden Delicious, Red Delicious, Elstar, and Cox's Orange apples were not affected by 52 weeks of storage in controlled atmospheric conditions. Chlorogenic acid and total catechins decreased slightly in Jonagold apples. Total catechin concentration decreased slightly in Golden Delicious, but chlorogenic acid concentrations remained stable. After 25 weeks of cold storage, there was no decrease in chlorogenic acid in any variety of apple, but catechin content decreased slightly in Golden Delicious, Elstar, and Cox's Orange apples. Both types of storage had no effect on antioxidant activity in any variety of apple examined. Another group looked specifically at the effects of storage on apple peel phenolics and found that storage at 0 Deg C for 9 months had little effect on phenolic content. Lattanzio et al. (2001) found that after 60 days of cold storage the concentration of total phenolics in the skin of Golden Delicious apples increased. After 100 days, the total phenolics in the skin began to decrease, but even after 200 days in storage, the total phenolics were similar to those at the time of harvest.

  Processing:

 Processing of apples has been found to affect phytochemical content. Apple juice obtained from Jonagold apples by pulping and straight pressing had 10% of the antioxidant activity of fresh apples, while juice obtained after pulp enzyming had only 3% of antioxidant activity. After pulp enzyming, the juice contained 31% less phloridzin, 44% less chlorogenic acid, and 58% less catechin. Most of the compounds remained in the apple pomace [81]. Similarly, Guyot et al. (2003) found that 42% of total phenolics were extracted in the juice, leaving over half the total phenolics in the apple pomace. They found that hydroxycinnamic acids and dihydrochalcones showed the greatest extraction yields in the juice, 65% and 80 % respectively. Procyanidins had the lowest yield in the juice (32%). Apple phenolics, especially procyanidins, have been found to bind with cell wall material, which could lead to the decreased levels of polyphenols found in apple juices.

 Apple pomace is a major waste product accumulated mainly during apple juice processing. Phloridzin, chlorogenic acid, epicatechin, and quercetin glucosides have all been isolated from apple pomace. These phenolics isolated from apple pomace have been found to have high antioxidant activity suggesting that apple pomace may have dietary health benefits and commercial use [84]. Millions of pounds of waste apple peels are generated in the production of applesauce and canned apples in New York State each year. Since apple peels contain a majority of the antioxidants when compared to the flesh, apple peels have the potential to be a value-added ingredient in food products. Apple peels were blanched and then dried under a variety of conditions (oven dried at a range of temperatures between 40¡ã and 80¡ã, air dried, or freeze dried). The freeze-dried samples had the greatest total phenolic and flavonoid content, and the total phenolic and flavonoid was actually greater than in the fresh peels. The apple peel powder had strong antioxidant activity and also greatly inhibited cancer cell proliferation.

  Conclusion:

 In numerous epidemiological studies, apples have been associated with a decreased risk of chronic diseases such as cardiovascular disease, cancer, and asthma. In vitro and animal studies have demonstrated that apples have high antioxidant activity, can inhibit cancer cell proliferation, decrease lipid oxidation, and lower cholesterol, potentially explaining their role in reducing risk of chronic disease. Apples contain a wide variety of phytochemicals, many of which have been found to have strong antioxidant activity and anticancer activity. The interaction of the many apple phytochemicals warrants more study as researchers attempt to further explain the mechanism behind the apple's ability to reduce risk of chronic disease. Recent research has shown that apples do contain bioavailable phytochemicals, although more work is needed to better understand the bioavailability of phytochemicals within the apple matrix as opposed to pure phytochemicals.

 Many factors affect the phytochemical profile of apples, and are important to consider as one attempts to understand and maximize the health benefits of apples. Phytochemical concentrations vary greatly between different cultivars. The level of some phytochemicals varies during maturation of the fruits in response to available light, stage of fruit development and to some types of fertilization. In general, storage of apples does not seem to greatly affect apple phytochemicals, but the processing of apples for juice results in a very significant decrease in phenolics. Processed apple peels retain their phenolic and flavonoid compounds activity and therefore may be used as a value-added ingredient with potent antioxidant activity.

 The potential health benefits of apples are numerous. Regular consumption of fruits and vegetables, including apples, as part of a healthy diet may aid in the prevention of chronic disease and maintenance of good health.


   Health benefits of apples: epidemiological evidence
 

  Anti-aging:

 Apple polyphenols show anti-cancer benefits, and may prevent or treat other age-related diseases including heart disease, Alzheimer's Disease, stroke, diabetes, and mental decline.

 Apple juice concentrate (AJC) prevents the increase in oxidative damage to brain tissue and decline in cognitive performance,contributes to the decline in cognitive performance during normal aging and in neurodegenerative conditions such as Alzheimer's disease.
 These findings provide further evidence that the antioxidant potential of Apple Extracts can compensate for dietary and genetic deficiencies that otherwise promote neurodegeneration.

  Anti-allergic results:

 Recent Research evaluate the anti-allergic effect of apple condensed tannins (ACT) in patients with atopic dermatitis (AD) as a pilot study. An ACT supplement given to the patients at oral doses of 10 mg/kg per day for 8 weeks reduced the inflammation, lichenification, cracking, itching, sleep disturbance and peripheral blood eosinophil counts. Itching and sleep disturbance scores after ACT supplement even for 2 weeks were significantly decreased compared with the control group. The results suggest that ACT has an anti-allergic effect and that its use improved the symptoms of AD. The oral administration of ACT significantly inhibited the ear swelling responses,result proved that apple extracts has an antiallergic effect on type I allergic symptoms.

  Antioxidant activity:

 Apples, and especially apple peels, have been found to have a potent antioxidant activity and can greatly inhibit the growth of liver cancer and colon cancer cells. The total antioxidant activity of apples with the peel was approximately 83 umol vitamin C equivalents, which means that the antioxidant activity of 100 g apples (about one serving of apple) is equivalent to about 1500 mg of vitamin C. However, the amount of vitamin C in 100 g of apples is only about 5.7 mg. Vitamin C is a powerful antioxidant, but this research shows that nearly all of the antioxidant activity from apples comes from a variety of other compounds. Vitamin C in apples contributed less than 0.4% of total antioxidant activity.

  Antiproliferative activity:

 Apples have been shown to have potent antiproliferative activity in several studies. When Caco-2 colon cancer cells were treated with apple extracts, cell proliferation was inhibited in a dose-dependent manner reaching a maximum inhibition of 43% at a dose of 50 mg/mL. The same trend was seen in Hep G2 liver cancer cells with maximal inhibition reaching 57% at a dose of 50 mg/mL. Eberhardt et al. proposed that it is the unique combination of phytochemicals in the apples that are responsible for inhibiting the growth of tumor cells. Apples had the third highest antiproliferative activity when compared to eleven other commonly consumed fruits.

 Different varieties of apples had different effects on liver cancer cell proliferation. At a dose of 50 mg/mL, Fuji apple extracts inhibited Hep G2 cell proliferation by 39% and Red Delicious extracts inhibited cell proliferation by 57%. Northern Spy apples had no effect on cell proliferation. Apples without peels were significantly less effective in inhibiting Hep G2 cell proliferation when compared to apples with the peel, suggesting that apple peels possess significant antiproliferative activity. Wolfe et al. demonstrated that apple peels alone inhibited Hep G2 cell proliferation significantly more than whole apples. For example, apple peels from Idared apples had an EC50 of 13.6 mg/mL whereas the whole apple had an EC50 of 125.1 mg/mL. The EC50 refers to the dose of the apple that is required to inhibit cell proliferation by 50%.

 There has been some concern that apple antioxidants do not directly inhibit tumor cell proliferation, but instead they indirectly inhibit cell proliferation by generating H2O2 in reaction with the cell culture media. However, more recently it has been reported that apple extracts did not generate H2O2 formation in WME, DMEM, or DMEM/Ham F12 media, and H2O2 addition to culture medium did not inhibit Hep G2 cell proliferation or Caco-2 colon cancer cell proliferation. Additionally, the addition of catalase did not block the antiproliferative activity of apple extracts.

  Asthma and pulmonary function:Apple Polyphenols and Asthma:

 Apple consumption has been inversely linked with asthma and has also been positively associated with general pulmonary health.

 In a recent study involving 1600 adults in Australia, apple intake showed a stronger inverse relationship with asthma. This latter effect was most clear in subjects who consumed at least two apples per week. Onion, tea, and red wine consumption were not related to asthma incidence, suggesting an especially beneficial effect of apple flavonoids.

 Apple intake and orange intake were both associated with a reduced incidence of asthma in the Finnish study involving 10, 000 men and women. Flavonoid intake in general was associated with a lower risk of asthma, and the association was attributed mainly to quercetin, hesperitin, and naringenin. Other fruits and vegetables, such as onions, grapefruit, white cabbage, and juices, were not associated with a decreased risk in asthma.

 In a study of over 13,000 adults in the Netherlands, it was found that apples might beneficially affect lung function. Apple and pear intake was positively associated with pulmonary function and negatively associated with chronic obstructive pulmonary disease. Catechin intake was also associated with pulmonary function and negatively associated with chronic obstructive pulmonary disease, but there was no association between tea, the main source of catechins, and chronic obstructive pulmonary disease [28]. A study of approximately 2500 middle aged (45~59 yrs) Welsh men also demonstrated a beneficial effect of apple consumption on lung function. Lung function was measured as forced expiratory volume (FEV) in one second, and was positively correlated with citrus fruit, fruit juice/squash, and apple consumption. However, the association with citrus fruit and fruit juice/squash lost significance after adjustment for smoking. Apple consumption remained positively correlated with lung function after taking into account possible confounders such as smoking, body mass index, social class, and exercise. Participants who consumed five or more apples per week had a significantly greater FEV of 138 mL when compared to those who did not consume apples.

  Cancer:

 Several studies have specifically linked apple consumption with a reduced risk for cancer, especially lung cancer. In the Nurses' Health Study and the Health Professionals' Follow-up Study, involving over 77,000 women and 47, 000 men, fruit and vegetable intake was associated with a 21% reduced risk in lung cancer risk in women, but this association was not seen in men. Very few of the individual fruits and vegetables examined had a significant effect on lung cancer risk in women, however apples were one of the individual fruits associated with a decreased risk in lung cancer. Women who consumed at least one serving per day of apples and pears had a reduced risk of lung cancer. Of the men involved, there was no association seen between any individual fruit or vegetable and lung cancer risk.

 In a case control study in Hawaii, it was found that apple and onion intake was associated with a reduced risk of lung cancer in both males and females. Smoking history and food intake was assessed for 582 patients with lung cancer and 582 control subjects without lung cancer. There was a 40~50% decreased risk in lung cancer in participants with the highest intake of apples, onions, and white grapefruit when compared to those who consumed the lowest amount of these fruits. The decreased risk in lung cancer was seen in both men and women and in almost all ethnic groups. No associations were seen with red wine, black tea or green tea. Both onions and apples are high in flavonoids, especially quercetin and quercetin conjugates. Le Marchand et al. found an inverse association between lung cancer and quercetin intake although the trend was not statistically significant. Interestingly, the inverse association seen between apple and onion intake and lung cancer were stronger for squamous cell carcinomas than for adenocarcinomas.

 In a Finnish study involving 10,000 men and women and a 24-year follow-up, a strong inverse association was seen between flavonoid intake and lung cancer development. In the sampled population, the mean flavonoid intake was 4.0 mg per day, and 95% of the total flavonoid intake was quercetin. Apples and onions together provided 64% of all flavonoid intake. The reduced risk of lung cancer associated with increased flavonoid consumption was especially strong in younger people and in nonsmokers. Apples were the only specific foods that were inversely related to lung cancer risk. Since apples were the main source of flavonoids in the Finnish population, it was concluded that the flavonoids from apples were most likely responsible for the decreased risk in lung cancer.

 The relationship of dietary catechins and epithelial cancer was examined in 728 men (aged 65~84) as part of the Zutphen Elderly Study. Tea, a naturally high source of catechins, contributed 87% of the total catechin intake in this study, while apples contributed 8.0% of catechin consumption. It was found that total catechin and tea consumption did not have an effect on lung cancer, but apple consumption was associated with decreased epithelial lung cancer incidence. This supported the findings of the previous studies discussed, where apples were significantly inversely associated with lung cancer, and may suggest that catechins alone do not play have a effect against lung cancers. Other data from the Zutphen Elderly study showed an inverse association between fruit and vegetable flavonoids and total cancer incidence and tumors of the alimentary and respiratory tract. Again, tea flavonoids were not associated with a decrease in cancer risk.
 Catechins from apple, the major source of non-tea catechins, were also related to lung cancer incidence


  Cardiovascular disease:

 A reduced risk of cardiovascular disease has been associated with apple consumption. The Women's Health Study surveyed nearly 40,000 women with a 6.9-year follow-up, and examined the association between flavonoids and cardiovascular disease. Women ingesting the highest amounts of flavonoids had a 35% reduction in risk of cardiovascular events. Flavonoid intake was not associated with risk of stroke, myocardial infarction, or cardiovascular disease death. Quercetin did not have any association with cardiovascular disease, cardiovascular events, myocardial infarction or stroke. However, both apple intake and broccoli intake were associated with reductions in the risk of both cardiovascular disease and cardiovascular events. Women ingesting apples had a 13~22% decrease in cardiovascular disease risk.

 In a Finnish study examining flavonoid intake and coronary mortality, it was found that total flavonoid intake was significantly inversely associated with coronary mortality in women, but not in men. Apple and onion intake was also inversely associated with coronary mortality, especially in women. Data collected from this same cohort study also showed the effect of quercetin and apple intake on cerebrovascular disease. Those who had the highest consumption of apples had a lower risk of thrombotic stroke compared to those who consumed the lowest amounts of apples. Onion intake and quercetin intake were not associated with thrombotic stroke or other cerebrovascular diseases.

 Apple and wine consumption was also inversely associated with death from coronary heart disease in postmenopausal women in a study of nearly 35,000 women in Iowa. The intakes of catechin and epicatechin, both constituents of apples, were strongly inversely associated with coronary heart disease death. Although total catechin intake was inversely associated with coronary heart disease mortality, Arts et al (2001) found that tea catechins were not associated with coronary heart disease mortality in postmenopausal women. Apple catechins may be more bioavailable than the catechin and epicatechin gallates commonly found in teas.

 The relationship between flavonoids and risk of coronary heart disease were also examined as part of the Zutphen Elderly Study. Flavonoid intake was strongly correlated with a decreased mortality from heart disease in elderly men and also negatively correlated with myocardial infarction. Tea was the main source of flavonoids in this study and was also negatively correlated with coronary heart disease. Apple intake contributed to approximately 10% of the total ingested flavonoids and was also associated with a reduced risk of death from coronary heart disease in men, however the relationship was not statistically significant.

  Cholesterol:Cholesterol-lowering effects

 The range of concentrations of phenolic classes in fresh apple extracts was: hydroxy methyl furfural, n.d.; phloridzin, 11-17%; cinnamates, 3-27%; anthocyanins, n.d.-42%; flavan-3-ols, 31-54%; flavonols, 1-10%. The ability of compounds in apple juices and extracts from fresh apple to protect LDL was assessed using an in vitro copper catalyzed human LDL oxidation system.

 Fruits and their juices contain phytochemicals that inhibit in vitro low-density lipoprotein (LDL) oxidation,the observed effect on LDL might be associated with reduced CAD risk and supports the inclusion of apple juice in a healthy human diet.
 Results clearly demonstrate that apple, but not wine polyphenols extract, dose-dependently decreases the esterification of cholesterol and the enterocyte secretion of lipoproteins.

 Diets supplemented with apples and to a less extent with peaches and pears have improved lipid metabolism and increased the plasma antioxidant potential especially in rats fed with added cholesterol. The highest content of biologically active compounds and the best results in the experiment on rats makes apple preferable for dietary prevention of atherosclerosis and other diseases.

 Some of the apple's protective effect against cardiovascular disease may come from its potential cholesterol-lowering ability. Aprikian et al. (2001) found that when cholesterol fed rats were supplemented with lyophilized apples, there was a significant drop in plasma cholesterol and liver cholesterols and an increase in high-density lipoproteins (HDL). Furthermore, they found that cholesterol excretion increased in the feces of rats fed apples, suggesting reduced cholesterol absorption. In a second study, a similar cholesterol lowering effect was seen in cholesterol fed rats when rats were fed apples, pears, and peaches. Apples had a greater cholesterol lowering affect than the other two fruits. The three fruits also increased the plasma antioxidant potential, with apple having the greatest effect. Apples, pears, and peaches all had similar fiber content, but apples contained more phenolic compounds suggesting that perhaps the phenolics in apples contribute to this effect.

 In obese Zucker rats, apple consumption lowered cholesterol and low-density lipoproteins (LDL), however in lean rats, apple consumption did not change cholesterol levels. In rats supplemented with cholesterol, apple pomace fiber and sugar beet fiber, the plasma lipids were significantly lower than in rats without the dietary fiber. Rats fed sugar beet pulp fiber and apple pomace fiber, but not fed cholesterol, had no change in lipids, suggesting that these sources of dietary fiber have hypolipidemic effects only in rats fed cholesterol. The sugar beet pulp fiber and the apple pomace fiber did not have an effect of lipid peroxides.

 Aprikian et al. in more recent studies, found that combined apple pectin and apple phenolic fractions lowered plasma and liver cholesterol, triglycerides, and apparent cholesterol absorption to a much greater extent than either apple pectin alone or apple phenolics alone. This work suggests that there is a beneficial interaction between fruit fiber and polyphenolic components and also supports the benefits of eating whole fruits as opposed to dietary supplements.

  Diabetes and weight loss:

 Not only may apples help decrease the risk of heart disease, cancer, and asthma, but apple consumption may also be associated with a lower risk for diabetes. In the previously discussed Finnish study of 10,000 people, a reduced risk of Type II diabetes was associated with apple consumption. Higher quercetin intake, a major component of apple peels, was also associated with a decreased risk in type II diabetes. Myrectin and berry intake were also associated with a decreased risk in type II diabetes, but onion, orange, grapefruit and white cabbage intake were not associated with a lowered risk.

 Apple and pear intake has also been associated with weight loss in middle aged overweight women in Brazil. Approximately 400 hypercholestemic, but nonsmoking, women were randomized to one of three supplement groups: oat cookies, apples or pears, and each subject consumed one of each supplement three times per day for twelve weeks. The participants who consumed either of the fruits had a significant weight loss after 12 weeks of 1.21 kg, whereas those consuming the oat cookies did not have a significant weight loss. Those consuming fruit also had a significantly lower blood glucose level when compared to those consuming the oat cookies.

 Higher quercetin intake, a major component of apple peels, was also associated with a decreased risk in type II diabetes.

 Phloridzin (PHZ) is an antidiabetic agent that is found primarily in apple peels,scientific research proved that The weight of white adipose tissue in MKR mice was decreased in response to PHZ treatment,fat pad weights decreased by 27 and 30%, respectively


  Hair Regrowth and apple polyphenol extract:

 Researchers in China have found that apple polyphenol extract, specifically procyanidin B-2, is extremely effective in regrowing hair in human male test subjects over 4 to 6 months.
 These impressive results were obtained when subjects with male pattern baldness used topical apple polyphenol extract in 2 randomized double-blind clinical trials.
 Procyanidin B-2 therapy shows potential as a promising cure for male pattern baldness.
 The maximum growth-promoting activity for hair epithelial cells with procyanidin B-2, an epicatechin dimer, reached about 300%,

 Procyanidins are a family of condensed tannins we have identified in apples, which act as a hair-growing factor in the murine model both in vitro and in vivo,After 12 months of use, 71% of the subjects showed an increased number of hairs in the designated scalp area relative to pre-trial measurements.

 Forskolin, an adenylate cyclase activator, promotes hair epithelial cell growth and boosts the growth-promoting effect of procyanidin B-2.
 

  Inhibition of lipid oxidation:

 Addition of apple phenolics to human serum decreased diphenylhexatriene-labeled phosphatidylcholine (DPHPC) oxidation in a dose dependent manner. DPHPC is incorporated into low-density lipoprotein (LDL), high-density lipoprotein and very low-density lipoprotein (VLDL) fractions and is an indicator of oxidation. Apple ingestion led to a decrease in DPHPC oxidation, reflecting the apples antioxidant activity in vivo. The protective effects of apples on LDL oxidation reached its peak at three hours following apple consumption and returned to baseline levels by 24 hours. Diphenylhexatriene labeled propionic acid (DPHPA) binds to serum albumin and is a good measure of oxidation within the aqueous phase of human serum. Mayer et al. (2001) also found that consumption of apples also led to a decrease in albumin DPHPA oxidation, reaching peak activity at 3 hours.

 Although apple juice typically contains less phenolics than whole apples, it is still a widely consumed source of dietary antioxidants. Pearson et al examined the effects of six commercial apple juices and Red Delicious apples (whole apples, peels alone, and flesh alone) on human LDL oxidation in vitro. LDL oxidation was measured using headspace analysis of hexanal produced from copper-induced lipid oxidation in vitro. The dose of the apple juices and whole apple, apple peel and apple flesh, were standardized for gallic acid equivalents, and each LDL solution was treated with 5 ¦ÌM gallic acid equivalents for each apple sample. LDL oxidation inhibition varied greatly between brands of fruit juice, ranging from 9 to 34% inhibition and whole apples inhibited LDL oxidation by 34%. Apple peels inhibited LDL oxidation by 34%, while the flesh alone showed significantly less inhibition (21%).

 Rats fed apple juice also had a decreased level of malondialdehyde (MDA), a marker of lipid peroxidation. Quercetin, a major flavonoid in apples, had no effect on lipid oxidation when ingested by rats, suggesting that quercetin alone is not responsible for the apple's ability to inhibit lipid oxidation. Other antioxidants and the interaction between the different apple antioxidants, including quercetin, may contribute to the antioxidant activity of apples. The effect of apple juice on lipid oxidation has also been examined in vivo in human subjects. In a study involving four women and one man, ingestion of high levels of a 1:1 mixture of apple juice and black currant juice increased the antioxidant status of the blood and decreased lipid oxidation. Glutathione peroxidase also increased in humans consuming apple juice. Plasma MDA decreased over the seven-day intervention period when the subjects ingested the highest dose of the apple juice and black currant mixture (1500 mL). Despite the antioxidant effect on lipoproteins, apple juice intake had a pro-oxidant effect on plasma proteins in both humans and rats.

  Other health effects:

 Aside from chronic disease, apples may be used to help combat other prevalent disease in the world. Recently it has been found that crude extracts from immature apples actually inhibited enzymatic activities of cholera toxin in a dose dependent manner. Additionally, apple extract reduced cholera toxin induced fluid accumulation in a dose dependent manner. The apple extracts were fractionated and each fraction was tested for inhibitory action on enzymatic activities of cholera toxin. The two apple extract fractions that contained highly polymerized catechins inhibited cholera toxin catalyzed ADP-ribosylation by 95% and 98%. The fraction containing non-catechin polyphenols caused only 3.5% inhibition and the fraction containing monomeric, dimeric, and trimeric catechins caused 39% inhibition.

  Summary:

 Based on these epidemiological studies, it appears that apples may play a large role in reducing the risk of a wide variety of chronic disease and maintaining a healthy lifestyle in general. Of the papers reviewed, apples were most consistently associated with reduced risk of cancer, heart disease, asthma, and type II diabetes when compared to other fruits and vegetables and other sources of flavonoids. Apple consumption was also positively associated with increased lung function and increased weight loss. Partially because of such strong epidemiological evidence supporting the health benefits in apples, there is increasing research using animal and in vitro models that attempts to more clearly explain these health benefits.

 Overall, the animal studies and in vitro work begin to define mechanisms by which apples may help prevent chronic disease. First, the strong antioxidant activity of apples may help prevent lipid and DNA oxidation. Cancer cell culture work has demonstrated that apples inhibit cell proliferation in vitro, which may contribute to the association of apple intake with decreased cancer risk. Apples significantly lowered lipid oxidation both in humans and rats and lowered cholesterol in humans. These effects, which may be attributed to both the phenolics and the dietary fiber found in apples, may partially explain the inverse association of apple intake and risk of cardiovascular disease.


   Frequently Asked Questions:

  Q: Are apple polyphenols safe?

 A: Yes. A study published in June 2004 in Food and Chemical Toxicology tested oral toxicity of apple polyphenol extracts at levels 200 times the recommended dosage for humans. Researchers reported "no significant hematological, clinical, chemical, histopathological, or urinary effects" even at these extreme dosages.
 Apple polyphenol extracts are listed (as "apple essence, natural") in the FDA's approved additive/GRAS (Generally Recognized As Safe) database.

  Q: Why can't I just eat apples?

 A: It would be great if we could all get plenty of concentrated polyphenols from diet alone, but most research indicates most dietary polyphenols are poorly absorbed. In 1997, researchers is the Netherlands reported that "flavonoids (polyphenolic compounds) present in foods were considered non-absorbable because they are bound to sugars."

 A study at the Linus Pauling Institute concluded that "despite the high antioxidant capacity of individual apple polyphenols and apple extracts and the significant antioxidant effects of apple extract added to human plasma in vitro, ingestion of large amounts of apples by humans does not appear to result in equivalent in vivo antioxidant effects of apple polyphenols."

 Many of the studies on the health benefits of apples are actually testing potent apple polyphenol extracts, not whole apples. Apple polyphenol extracts are highly bioavailable and water-soluble.

 You can increase your intake of apple polyphenols by eating fresh apples (including the skin, where the highest concentrations are found), but unless you have your own apple trees, there is no guarantee that your fruit contains enough apple polyphenols.
 Worse, the apples at your grocery store are not fresh, and may have lost most of their polyphenol content before you buy them. All commercial apples in the U.S. are cold-stored in warehouses, most for many months. A study on apples published in 2004 found that "total phenolics and total antioxidant activity" decreased in the first three months of cold storage, and that "cold storage rapidly impoverishes these properties in skin." The same study reported "strong, time-related decreases over 6 mo of cold storage..."

 Most commercial apple products contain little or no polyphenols due to processing. Polyphenol content also varies greatly between apple varieties and fruit maturity. Relatively higher concentrations have been found in Granny Smith, Red Delicious, Rome Beauty, and Idared varieties.
 Chinese researchers report that immature apples, which are too bitter to eat, contain 10 times more apple polyphenols than mature apples. These immature apples are used to produce the high-concentrate apple polyphenol extracts.
 Surely, there is some benefit in increasing dietary intake of apples. There are serious questions, however, as to whether eating whole, cold-stored apples will substantially increase your absorption of these valuable polyphenols.

 Many of the studies on the health benefits of apples are actually using potent apple polyphenol extracts, not apples, in those studies.
 The use of standardized apple polyphenol extracts makes sense in terms of laboratory testing, but using the apple polyphenol extracts may also make sense for people wanting to realize the reported health benefits, for the following reasons:
 Apple extracts are the actual compounds showing the results in many of the available medical studies.

 The polyphenol bioavailability of apple peel powder extracts is far higher than from whole apples, which must be digested to extract the phytochemicals.
 The concentration of polyphenols in apple peel extracts makes it possible to consume higher doses. (Many studies you will read report dose-dependent effects, with higher dosages providing greater benefits.)

 

   Apples:Witches Brew:

 Apples have long been associated with witches. As in Snow White, witches were said to have used apples to poison or to bewitch. In some parts of England, strong cider is still known as "witches' brew." When cut crosswise, a pentacle is visible inside the apple.

 Although no one type of fruit is specified in Genesis, in Christian folklore, the apple is portrayed as the fruit of knowledge eaten by the disobedient Eve and Adam.

 In 1657 Richard Jones, a 12-year-old boy in Shepton Mallet in the county of Somerset in England, was said to be bewitched by a girl who gave him an apple. Jones suffered fits, and neighbors said they saw him fly over his garden wall. The girl, Jane Brooks, was charged with witchcraft, convicted and hanged on March 26, 1658 (Guiley 1989 12).


   From Findings of Apple Procyanidin B-2:

  Procyanidin B-2, Extracted from Apples, Grows Hair in Clinical Trials:

 Late in 2000,Researchers presented their findings to the international community on the hair growing effects of apple polyphenols- specifically one known as procyanidin B-2.
 The researchers had spent years testing over 1,000 botanical extracts for hair growth properties. They identified two successful compounds- one from chardonnay grapes, and one extracted from unripe apples.
 A year before the landmark Marburg conference, tests were conducted on mouse and human skin cells.

 Here is what the cell culture tests revealed:

 

 The procyanidin B-2 fraction clearly outperformed the grape extract, and nearly doubled the hair growth activity of minoxidil. "Procyanidin B-2 purified from apples," stated the research team, "shows the highest activity of more than 300% relative to controls.":
 Promising results, indeed. Next came the in vivo mouse studies. Lab mice were shaved, then treated with procyanidin B-2, procyanidin C-1 (also from apples), minoxidil, and placebo. Results of these tests showed "extensive hair growth" for both procyanidins B-2 and C-1, as well as minoxidil.

  Investigation of topical application of procyanidin B-2 from apple to identify its potential use as a hair growing agent, Phytomedicine, 2000:

 In a double-blind placebo-controlled trial, nineteen men with male pattern baldness were studied with a daily topical application of a 1% procyanidin B-2 solution, extracted from apples. Ten other balding men served as controls, receiving a placebo solution. After 6 months, the study concluded:

 The increase in number of total hairs and terminal hairs in the procyanidin B-2 group subjects was significantly greater than controls
 78.9% of subjects showed an increased mean value of hair diameter
 "Procyanidin B-2 therapy shows promise as a cure for male pattern baldness."

  Procyanidin B-2, extracted from apples, promotes hair growth: a laboratory study, Br J Dermatol. 2002 Jan;146(1):41-51

 In this study, the researchers concluded that procyanidin B-2 acts to diminish protein kinase C isozymes, which play an important role in the hair growth cycle.
 Procyanidin B-2 seems to promote hair growth by downregulating PKC in both the anagen (active growth phase) and telogen (resting phase) of the hair follicle. When the anagen phase is prolonged, and the telogen phase is shortened, increased hair growth results.

 Two more clinical trials and a total of seven published studies have now confirmed the surprising hair growth-promoting effects of apple procyanidins. Here is a summary of those findings:
  Total Number of Hairs: Significantly Increased
  Total Number of Terminal Hairs: Significantly Greater
  Increase in Hair Diameter: 78.9% Positive
  Ratio of Thicker (terminal) Hairs: Significantly Higher
  Compared to Minoxidil: Up to 200% Better
  Hair Follicle Activation: Intensive

 


  Here are key findings:

 1. Multiple Procyanidins Produce Synergistic Results:

 First, a careful review of the data revealed that both procyanidin B-2 and procyanidin C-1 had profound effects on hair growth, but at different phases of the hair growth cycle. Further, the procyanidin B-3 fraction also showed significant results: even better than procyanidin B-2 in one testing phase.
 The first improvement to the formula was delivered- by enriching it with all three procyanidin oligomers- B-2, B-3 and C1.

 2. Apple Procyanidins are Dose-dependent in Nearly Every Study:

 The team then turned their attention to the concentration of the lab formula. Was a 1% solution- the amount used in the clinical trials- really the best possible strength for stimulating new hair growth?
 Based on months of cross-discipline research review of apple procyanidins and polyphenols, another clear trend emerged. In nearly every area of research, the effects of procyanidins were dose-dependent.
 When researchers treated breast cancer tumors with apple procyanidins, the effects were markedly enhanced at higher concentrations. In tests on colon cancer, skin cancer, Alzheimer's, and heart disease, the results were always the same: the higher the concentration, the better the results.
 Since procyanidins are thoroughly tested safe, and produce zero irritation or unwanted side effects, there seemed to be no reason to stop at a measly one percent. So they quadrupled the procyanidin strength of the new formula.


   Properties and effects of Polyphenol from Apple:

  1).  Suppresses the production of the melanin.
  2).  Suppresses the functioning of tyrosine enzymes.
  3).  Reliable results for whitening.
  4).  Used as an external cosmetic with apple polyphenol has the double,effect of protecting the skin and alleviating allergic dermatitis.
  5).  Prevents free radicals and ultraviolet ray damage to the skin.
  6).  Reliable sun-proof effects.
  7).  Applied as a sun lotion.
 


   Processing Method:Concentration of phenolics extracted from apples:

 The present invention also relates to the process of obtaining products used as food additives having enlarged concentrations of phenolics, the process involving extraction of phenolics from fruits, particularly from apples.

  A:Normal composition of Apple Polyphenols:  gallic acid, flavan-3ols, flavonols, phloridzin, cinnamates, hydroxymethyl furfural and anthocyanins.

 It has been known in the prior art that certain compounds or ingredients, present in fruits, particularly in grapes and apples, possess various benefits for human health apart from the well known benefits of vitamins, minerals and other nutrients considered to be the main ingredients of fruits. The terms "phenolics" or "plant phenolics" have been developed and been adopted in the art for a class or type of these compounds because these compounds include in their formula a hydroxyl (OH) function attached to an aromatic carbon atom in analogy to the well known chemical phenol, or these compounds have a chemical structure closely related to or derived from a compound having an aromatic (phenolic) hydroxyl group. Usually plant phenolics have more than one aromatic (phenolic) hydroxyl group. Generally speaking, plant phenolics have antioxidant properties and have been shown in in vitro and in in vivo studies to have positive effects on the human cardio-thoracic condition. The phenolics isolated from fruits, primarily from apples, include gallic acid, flavan-3ols, flavonols, phloridzin, cinnamates, hydroxymethyl furfural and anthocyanins.

  B:Raw material and part used:

 Because of the richness of apples as a source of plant-phenolics and because of the availability of apple peel and core as a relatively economical raw material, efforts in accordance with the present invention to produce isolates containing high concentration of phenolics have been focused on apple peel and apple core serving as a source.
 


  C:Summary and Processing:

 It is an object of the present invention to obtain from fruits, and particularly from apples, an extract which is rich in natural phenolics of the fruit and which is utilized as a supplement or additive in various food products.

 It is another object of the present invention to obtain from fruits, and particularly from apples, an extract which is rich in natural phenolics of the fruit and which does not impart an unnatural or undesired taste component to the food product in which it is used. It is still another object of the present invention to provide food products such as beverages, dairy products, frozen products, jams, jellies, preserves, and confectionary products which have an enlarged concentration of phenolics that have been extracted from fruits, particularly from apples, in accordance with the present invention.

 The foregoing objects and advantages are attained by a product or products that is obtained by extracting the fruit, or parts of the fruit such as peels and or cores with hot water in a temperature range of approximately 65 to 93 Deg C. (150 to 200 Deg F.), followed by depectinization of the extract with a pectinase enzyme, preferably at an elevated temperature of approximately 38 to 57 deg C. (100 to 135 deg F.) until test taken for pectin is substantially negative. The pectinase enzyme is then deactivated by heating the mixture to approximately 60 to 93 deg C. (140 to 200 deg F.) and the aqueous solution/suspension is filtered to yield discardable solids and an aqueous filtrate. Polyvinylpolypyrrolidone (PVPP) adsorbent is then added to the filtrate aqueous solution and the mixture is agitated to extract by adsorption of the plant phenolics contained in the aqueous phase. The polyvinylpolypyrrolidone (PVPP) adsorbent containing adsorbed plant phenolics is then collected by filtration, centrifugation or like method. The aqueous filtrate at this stage is substantially devoid of recoverable plant phenolics but after concentration can still serve as useful product, primarily as a delivery vehicle for the plant phenolics obtained by the following additional process steps.

 The collected solid polyvinylpolypyrrolidone (PVPP) adsorbent containing adsorbed plant phenolics is then washed multiple times with water to remove solids other than the adsorbed plant phenolics. The plant phenolics are obtained from the PVPP adsorbent by treating the adsorbent with dilute sodium hydroxide (or other acceptable strong base) solution, to give an aqueous extract of the plant phenolics, having a concentration of approximately 400 to 5000 mg gallic acid equivalent per liter (GAE/L) of the extract. The polyvinylpolypyrrolidone (PVPP) adsorbent recovered by filtration can be regenerated for repeated use by careful washing with water until all base is substantially removed from it.

 The aqueous extract containing the plant phenolics can be further concentrated to give a liquid product with greater concentration of plant phenolics. Alternatively the aqueous extract is mixed with a nutritionally acceptable carrier, such as maltodextrin, rice dextrin, modified corn starch or other carrier, and the mixture is converted to a solid by spray drying or like drying process effective to yield a solid product. When in a solid form, such as the spray dried product obtained from the aqueous extract, the concentration of phenolics depends on the amount of carrier (if any) or carriers added and on the moisture content of the solid. Preferably the spray dried solid product contains approximately 10 mg or more gallic acid equivalent (GAE) per gram of solid (1% by weight). When the aqueous extract is concentrated but not dried completely, it typically contains approximately 50,000 to 200,000, preferably approximately 100,000 mg GAE/L.

 The liquid concentrate, dried solid product or their solutions can be added to diverse types of food products, such as beverages, dairy products, frozen products, jams, jellies, preserves, and confectionary products to provide or enrich the products with fruit phenolics.

 The features of the present invention can be best understood together with further objects and advantages by reference to the following description, taken in connection with the accompanying drawings.
 

  Measurement of Plant-Phenolic Content:

 The Folin-Ciocalteau method is used to measure the phenolic content of the products using gallic acid as a standard. Total phenolic content was determined colorimetrically, using a Beckman DU-50 spectrophotometer. The molecular weight of gallic acid is 170.1. A standard solution of gallic acid at 0.01 M is made by completely dissolving with stirring 1.701 grams of gallic acid in 1 liter distilled water. Diluted solutions of gallic acid in millimolar concentrations ranging from 0.00 mM to 0.2 mM are created as standards from distilled water and this standard solution. A sodium bicarbonate solution of 0.71 M strength is made by dissolving 59.64 grams of the substance in 1 liter of distilled water.

  Folin-Ciocalteau Assay:

 0.1 gram phenolic substance (plant extract) to be assayed is weighed out and diluted to 10 grams with water and further diluted with another 6 grams of 0.71 M sodium bicarbonate. This mixture is allowed to react with 0.1 gram Folin-Ciocalteau reagent for 2 hours. A colored complex develops during this reaction period. The colored reaction medium is then measured for absorbance at 660 nm using the spectrophotometer. By comparison with an absorbance versus gallic acid equivalent per liter (GAE/l) curve that has been obtained by measurement of the standard solutions (standard curve) the concentration of plant phenolics in the assayed product is obtained (expressed as mg Gallic Acid Equivalents (GAE)/Liter). The phenolic standard gallic acid, sodium bicarbonate, and Folin-Ciocalteau reagent were obtained from Sigma Chemical Company, St Louis, Mo.


   Apple Polyphenol and Its Application to Tooth coating composition:

 Accordingly, an object of the invention is to provide a tooth coating composition having a quick drying property as demanded by general consumers and being excellent in the durability while having the merits of tooth coating compositions of prior art.

 As the result of making intensive investigations in view of the above-described circumstances, the present inventors have found that by using specific mica titanium for a tooth coating composition using shellac as the main body, a tooth coating composition, which does not become white turbid for a long time, has a quick drying property, and is excellent in the durability, is obtained and have accomplished the present invention.

  Then, the present invention described below in detail:
 

 Shellac used in the invention is a resin, which has actual results of being used for foods and has a very high safety. In the tooth coating composition of the invention, the shellac is used as a coat-forming component. The content of such a shellac in the total composition is preferably in the range of from 1% by weight to 20% by weight. When the content of shellac is less than 1% by weight, the coat is too brittle and thus the composition cannot be used as a tooth coating composition. Also, when the content thereof exceeds 20% by weight, the viscosity of the coating liquid is increased, whereby it becomes difficult to thinly coat the composition on teeth and also the drying property becomes inferior. The particularly preferred content of shellac is from 5% by weight to 15% by weight.

 In addition to shellac as the coat-forming component, one kind or a combination of two or more kinds of other resins, high molecular materials, and dental cements can be added to the composition at a suitable amount. By adding such material(s), the preferred effects of more improving the luster of the coat and more improving the dispersion of mica titanium or pigments can be expected.
 Examples of such a resin include an acrylic resin, a vinyl acetate resin, an alkyd resin, a vinyl chloride resin, a silicone resin, a fluorine resin, rosin, etc.
 Examples of the high molecular material include vinylon, nylon, polyvinyl alcohol, polyvinyl pyrrolidone, polyvinyl butyral, polybutene, polyethylene, polypropylene, polyisoprene, cellulose ethers, nitrocellulose, ester gum, viscose rayon, polysaccharide, etc.
 


 Furthermore, examples of the dental cements include zinc phosphate cement, carboxylate cement, glass ionomer cement, zinc oxide euginol cement, silicate cement, etc.

 Mica titanium is a substance obtained by coating a mica powder with a thin film of titanium oxide, and fundamentally has been frequently used as a pigment but in the invention, by compounding mica titanium as a coat-strengthening agent, the tooth coating composition excellent in the durability after coating is obtained. Also, by controlling the thickness of the titanium oxide film of the mica titanium, it is possible to obtain an interference color such as yellow, red, blue, green, etc., whereby the tooth coating composition giving a good aesthetic appearance is obtained.

 The compounding amount of such a mica titanium in the whole composition is preferably from 0.5% by weight to 30% by weight. When the content of mica titanium is less than 0.5% by weight, the strength of the coat is lowered and the desired durability is not obtained. On the other hand, the content thereof exceeds 30% by weight, the dispersibility thereof in the solution becomes inferior, also, not only after coating, the evaporation of the solution is delayed to reduce the drying property, but also after coating, a rough-feeling sense of incongruity occurs in the mouth. Particularly preferred compounding amount of mica titanium is from 2% by weight to 15% by weight of the whole composition.
 The mean particle size of mica titanium used in the invention is in the range of preferably from 5 um to 50 um, and more preferably from 10 um to 30 um. By using the mica titanium having the mean particle size of from 5 um to 50 um, a proper hiding power is imparted to the coat and further the using feeling in the mouth is improved.


 As the main solvent of the tooth coating composition of the invention, a lower alcohol-base solvent dissolving shellac is used. As the solvent, which is nontoxic to the human body and dissolves well shellac, there are ethanol, n-propanol, isopropanol, n-butanol, isobutanol, etc., and from the points of the dissolving property and the volatile property, ethanol is most preferred. In addition to the main solvent, as an auxiliary solvent, any solvent, which is safe for the human body and gives less stimulation in the mouth, may be used. For example, as an auxiliary solvent, there are water, propylene glycol, glycerol, etc. Propylene glycol and glycerol are also frequently used as the solvents for general cosmetics and are used for dissolving medical components and extracts.
 To the tooth coating composition of the invention can be added a chemical having an anti-cariogenic action. As such a chemical having an anti-cariogenic action, there are sodium fluoride, sodium monofluorophosphate, stannous fluoride, and polyphenol-containing vegetable extract.

 There are actual results that sodium fluoride, sodium monofluorophosphate, or stannous fluoride is properly compounded in dentifrices as a medical component having an anti-cariogenic action and many products are on the market. Also, it is known that the polyphenol-containing vegetable extract has an antimicrobial action to the S. Mutans bacteria, which is a decayed tooth bacteria, and the extract is considered to be a very effective dental carries preventing agent.
 Practical examples of the polyphenol-containing vegetable extract include one or more extracts selected from the group consisting of a fig extract, a hydrangea tea extract, an oolong tea extract, a tea extract, a grape seed extract, a grape rind extract, a blue berry extract, an apple extract, a eucalyptus extract and a rosemary extract.

 By compounding the above-described medicine having the anti-cariogenic action with the tooth coating composition of the invention, without making a troublesome action such as teeth polishing such as brushing, etc., the dental caries preventing effect can be expected.

 Also, the tooth coating composition of the invention can, if necessary, contain various coloring agent. Examples of such a coloring agent include zinc oxide, titanium oxide, barium sulfate, mica, carbon black, white carbon, calcium hydrogenphosphate, calcium tertiary phosphate, hydroxy apatite, iron oxide, chromium oxide, magnesium oxide, calcium oxide, aluminum oxide, fish flakes, talc, calcium carbonate, magnesium carbonate, barium carbonate, and tar dyes.
 


 Furthermore, the tooth coating composition of the invention can contain, if necessary, various pharmaceutical components other than the above-described substances and also spicery, an antiseptic, a buffer, s pH controlling agent, a surface active agent, a dispersing agent, a plasticizer, a ultraviolet absorbent, a viscosity controlling agent, an antioxidant, etc.

 The pharmaceutical components include sodium azulenesulfonate, Epsilon-aminocaproic acid, allantoin, allantoin chlorohydroxy aluminum, allantoin dihydroxy aluminum, epidihydrocholestrin, dihydrocholesterol, sodium chloride, glycyrrhizinic acid, diammonium glycyrrhizinate, di-sodium glycyrrhizinate, tri-sodium glycyrrhizinate, di-potassium glycyrrhizinate, mono-ammonium glycyrrhizinate, beta-glycyrrhizinic acid, isopropyl methyl phenol, cetylpyridinium chloride, decalinium chloride, benzalkonium chloride, benzethonium chloride, alkyldiaminoethylglycine hydrochloride, chlorohexidine hydrochloride, tricrosane, ascorbic acid, sodium ascorbate, pyridoxine hydrochloride, dl-alpha-tocopherol acetate, dl-alpha-tocopherol nicotinate, zeolite, di-sodium dihydrogen pyrophosphate, sodium pyrophosphate, sodium hydrogenphosphate, sodium tertiary phosphate, sodium polyphosphate, polyethylene glycol, polyvinyl pyrrolidone, lysozyme chloride, copper chlorophyllin sodium, hinokitiol, polyoxyethylene lauryl ether, lauroylsarcosine sodium, etc.
 The above-described pharmaceutical components have the actual results of being compounded with dentifrices and are preferred materials as the materials of being used in the mouth. As the pharmaceutical effects thereof, there are, in addition of the prevention of dental caries, the prevention of halitosis, the prevention of the deposition of tartar, the prevention of gingivalise.gingivitis, the effect of removing nicotine, etc.

 In addition, as the dispersing agent described above, there is an N-methacrolylethyl-N,N-dimethylammoniume. alpha-N-methylcarboxybetainee.butyl methacrylate copolymer. The compound functions as a good dispersing agent.


   Phloridzin-rich phenolic fraction and use thereof as a cosmetic, dietary or nutraceutical agent:

 The present invention relates to a phenolic fraction from fruit and also to the process for obtaining this fraction. This extract rich in an antioxidant compound, phloridzin, can be used as a cosmetic, dietary or nutraceutical preparation.

 It is known that polyphenolic compounds are rela