Apples

Generic name: Malus Communis Poir., Malus Domestica Auct. Non Borkh.kasai, Malus Praecox (Pall.) Borkh., Malus Pumila Mill., Malus Sylvestris Amer. Auth., Non (L.) Mill., Pyrus Pumila (Mill.) K. Koch
Brand names: Apple

Usage of Apples

Increasing evidence from in vitro, in vivo, and epidemiological studies suggests that flavonoids found in apples may be protective against cancer, cardiovascular disease, diabetes, asthma, obesity, other chronic diseases, and overall mortality.(Boyer 2004, Knekt 2002, Lewis 2004, Schrenk 2009)

Beneficial health effects can be attributed to the phytochemicals, fructose, and dietary fiber found in apples. Apples are low in calories, fat, and sodium, characteristics that contribute positively to cardiovascular health.(Lewis 2004)

Raw apples are a good source of dietary soluble and insoluble fiber, two-thirds of which are found in the peel.(Lewis 2004, Sampson 2002) Soluble fiber, such as pectin, may help lower cholesterol levels and normalize blood glucose and insulin levels.(Brouns 2012, Knopp 1999, Marlett 2002) Pectin has also been used to treat diarrhea. (For further information, see the Pectin monograph.) Insoluble fiber promotes bowel regularity and helps move food quickly through the digestive tract; it may therefore be effective in the treatment of constipation, diverticulosis, and some types of cancer.(Marlett 2002) The antioxidant activity, along with effects of the fiber content, have been shown to influence multiple mechanisms relevant for cancer prevention and cardiovascular protection.(Boyer 2004)

Allergic disorders

Animal and in vitro data

Apple extract and procyanidin extract inhibited histamine release in in vitro allergic models.(Kanda 1998) It is postulated that this effect is mediated by inhibition of calcium influx and histamine release. An in vivo study in mice suggested that apple polyphenol extract administered orally has an antiallergic effect on type 1 allergy symptoms.(Akiyama 2000)

Clinical data

In a double-blind clinical trial using apple polyphenol extract 500 mg twice daily (produced commercially from unripe apples) in pediatric patients with atopic dermatitis, itching score decreased compared with placebo.(Kasai 1996)

In another study, 33 patients 15 to 65 years of age with moderate or severe persistent allergic rhinitis were treated with no, low-, or high-dose apple polyphenols. Significant improvements were observed in sneezing attacks and nasal discharge in the high-dose group and in sneezing attacks in the low-dose group compared with prior to treatment; however, there were no significant differences between the high- or low-dose groups and the control group. In addition, the percentage of patients who showed improvement in swelling in the nasal turbinates was higher in the polyphenol-treated groups. It was concluded that apple polyphenols are effective in alleviating symptoms of persistent allergic rhinitis.(Enomoto 2006)

A systematic review investigated the effects of dietary interventions on pollen-related food allergies in adults. In the 2 studies evaluating apples (N=92), increasing doses of Golden Delicious apple were employed as oral immunotherapy. Tolerance to apple developed in 63% to 81% of patients, 98% of whom were able to eat certain other cross-reacting fruits in the Rosaceae family by study end (8 months). Limited data identified 3 patients with mild symptoms to raw, but not cooked, carrot or apple. Low allergenic apple cultivars included Santana and Elise apples, whereas Golden Delicious and G-198/Orim were the most allergenic. The quality of all studies was very low.(Lyons 2018)

Anti-inflammatory activity

Anti-inflammatory mechanisms for apple have been demonstrated in several studies.(Jung 2009, Kahle 2005, Puel 2005, Setorki 2009, Zessner 2008) However, some studies have shown no effect on inflammatory biomarkers or have documented a significant genotype-based association.(Barth 2012, Shoji 2017)

In vitro data

In vitro assays have revealed anti-inflammatory mechanisms related to inhibition of both cyclooxygenase 2 (COX-2) and lipoxygenase enzymes via several synergistic compounds.(Jensen 2014)

Clinical data

Symptom improvement in patients with arthritis, allergic rhinitis, atopic dermatitis, and acute gastritis has been demonstrated in clinical trials.(Enomoto 2006, Freedman 2016, Jensen 2014, Kasai 1996)

Antioxidant activity

Antioxidant activity has been noted to be much higher for the apple peel than the flesh.(Vieira 2009, Wolfe 2003) The increase in human plasma antioxidant capacity after apple consumption appears likely due to a metabolic effect of the fructose in apples on urate, an important endogenous antioxidant in plasma, and not necessarily a result of apple-derived antioxidants or plasma polyphenol levels.(Boyer 2004, Lotito 2004a, Lotito 2004b, Lotito 2006, Wruss 2015) Antioxidant effects have been documented in some additional studies(Avci 2007, Chai 2012, Jensen 2014, Tenore 2019a) but not in others.(Auclair 2010, Bondonno 2018, Zhu 2018)

Clinical data

In a pharmacokinetic study of 35 healthy volunteers (19 to 42 years of age), consumption of 500 mL of unfiltered, organic apple juice led to a significant average increase in total plasma phenolic content of 10% to 19% within 6 hours compared to overnight fast samples (P<0.003); concentrations and time to peak were highly variable among participants. The juice contained 1,080 mg of polyphenols, 13 g of glucose, and 40 g of fructose. Antioxidant capacity of plasma samples displayed 2 peak time periods: a 17% increase at 1 hour post consumption, a 13% decrease within 2 hours, and more than a 17% increase again at 6 hours. The antioxidant capacity could not be correlated to polyphenolic levels.(Wruss 2015)

Arthritis

In vitro data

In vitro assay testing of blood drawn from 12 healthy volunteers with moderate loss of joint range of motion and associated chronic pain revealed dose-dependent antioxidant activity, reduced reactive oxygen species from polymorphonuclear cells, and anti-inflammatory mechanisms related to inhibition of COX-2 and lipoxygenase enzymes.(Jensen 2014)

Clinical data

In the previously described small, open-label pilot study of healthy volunteers with moderate loss of joint range of motion and associated chronic pain (N=12), consumption of dried apple peel powder (1.5 g 3 times daily for 12 weeks) improved range of motion, antioxidant parameters, and chronic pain. Shoulder and lumbar joints improved more rapidly than cervical, thoracic, and hip joints.(Jensen 2014)

Asthma and pulmonary function

Apple consumption has been inversely linked with asthma and has also been positively associated with general pulmonary health.(Boyer 2004)

Clinical data

A study from the United Kingdom surveying nearly 600 asthmatic patients and 900 nonasthmatic patients about diet and lifestyle showed total fruit and vegetable intake was weakly inversely associated with asthma, while apple intake showed a stronger inverse relationship with asthma, particularly in those who consumed at least 2 apples per week. Intake of other foods high in flavonoids, such as tea, red wine, and onion, was not related to asthma incidence.(Shaheen 2001)

In a large study in Finland involving 10,000 men and women, apple and orange intake was associated with a reduced incidence of asthma, whereas intake of other fruits and vegetables, such as onions, grapefruit, cabbage, and juices, was not.(Sesso 2003) Similarly, a study in Australia involving 1,600 adults showed apple and pear intake was associated with a decreased risk of asthma and a decrease in bronchial hypersensitivity, whereas a significant association between total fruit and vegetable intake and asthma risk or severity was not found.(Woods 2003)

Two studies have demonstrated a beneficial effect of apple consumption on lung function.(Butland 2000, Tabak 2001) One study of 13,000 adults in the Netherlands demonstrated that apple and pear intake was associated positively with pulmonary function and negatively with chronic obstructive pulmonary disease.(Tabak 2001) In the other study of 2,500 Welsh men, consumption of apples was positively correlated with forced expiratory volume in the first second of expiration (FEV1), even after adjustment for possible confounding factors such as smoking, body mass index (BMI), social class, and exercise. Participants who consumed 5 apples or more each week had a greater FEV1 compared with those who did not consume apples.(Butland 2000)

Cancer

Antioxidant activity, along with effects of apple fiber content, influence multiple mechanisms relevant for cancer prevention.(Boyer 2004, Ko 2005, Maffei 2007, Mayer 2001) These include antimutagenic activity,(Kahle 2005, McCann 2007, Miene 2009, Petermann 2009) modulation of carcinogen metabolism,(Kahle 2005) antioxidant activity,(Eberhardt 2000, Kahle 2005, Setorki 2009, Zessner 2008) anti-inflammatory mechanisms,(Jung 2009, Kahle 2005, Puel 2005, Setorki 2009, Zessner 2008) modulation of signal transduction pathways,(Kahle 2005) antiproliferative activity,(Eberhardt 2000, Liu 2001, Liu 2009, Nelson 1993, Sun 2002, Sun 2008, Wolfe 2003) and apoptosis-inducing activity.(Gerhäuser 2003, Liu 2009, Maldonado 2009) However, these studies suggest that apple or apple juice consumption results in only a brief transient increase in antioxidant capacity 0.5 to 6 hours after consumption.(Lotito 2004a, Lotito 2004b, Lotito 2006, Wruss 2015)

Clinical data

Breast cancer

Antioxidant activity, along with effects of apple fiber content, influence multiple mechanisms relevant for cancer prevention.(Boyer 2004, Ko 2005, Maffei 2007, Mayer 2001) These include antimutagenic activity,(Kahle 2005, McCann 2007, Miene 2009, Petermann 2009) modulation of carcinogen metabolism,(Kahle 2005) antioxidant activity,(Eberhardt 2000, Kahle 2005, Setorki 2009, Zessner 2008) anti-inflammatory mechanisms,(Jung 2009, Kahle 2005, Puel 2005, Setorki 2009, Zessner 2008) modulation of signal transduction pathways,(Kahle 2005) antiproliferative activity,(Eberhardt 2000, Liu 2001, Liu 2009,, Nelson 1993, Sun 2002, Sun 2008, Wolfe 2003) and apoptosis-inducing activity.(Gerhäuser 2003, Liu 2009, Maldonado 2009) However, these studies suggest that apple or apple juice consumption results in only a brief transient increase in antioxidant capacity 0.5 to 6 hours after consumption.(Lotito 2004a, Lotito 2004b, Lotito 2006, Wruss 2015)

An analysis of pooled data from 5 case-control studies identified a significant reduction in breast cancer risk associated with apple intake (odds ratio [OR]=0.79 [95% CI, 0.73 to 0.87]; P<0.001; no heterogeneity [I2=1%]). In contrast to case-control studies, no significant association was found among 3 cohort studies. Borderline significance was observed when combining both case-control and cohort studies (relative risk [RR]=0.89 [95% CI, 0.79 to 1]; P=0.047; I2=69%).(Fabiani 2016)

Colorectal cancer

Evidence indicates that regular consumption of 1 or more apples each day may reduce the risk of colon cancer.(Deneo-Pellegrini 1996, Fabiani 2016, Gallus 2005, Jedrychowski 2009, Jedrychowski 2010, Lee 2005, Michels 2006, Theodoratou 2007) In the Nurses' Health Study, the cohort of women who ate the most apples had a reduced risk of developing colorectal adenomas compared with those with the lowest apple intake.(Michels 2006) A pooled analysis of 8 case-control and cohort studies revealed a significant reduction in colorectal cancer risk associated with high apple intake, although heterogeneity was high (RR=0.72 [95% CI, 0.59 to 0.88]; P=0.001; I2=77%). When stratified by study type, however, significance was limited to only the case-control studies. Similarly, pooled analysis of data from 16 studies for all digestive tract cancers (ie, colorectal, oral cavity, esophageal, stomach) showed an inverse relationship between cancer risk and apple intake for case-control studies (OR=0.5 [95% CI, 0.36 to 0.69]; P<0.001; high heterogeneity [I2=90%]) but not cohort studies.(Fabiani 2016) In another case-control study in Korea, consumption of fruits, including apples, lowered the risk for colon cancer in men but not women.(Lee 2005)

Lung cancer

Also in the systematic review and meta-analysis, pooled analysis of 24 case-control and cohort studies identified a significant 12% reduction in lung cancer risk with high apple consumption (RR=0.88 [95% CI, 0.83 to 0.92]; P<0.001; moderate heterogeneity [I2=65%]). Stratification by study type, sex, and smoking status revealed significant reductions for both case-control (P=0.001) and cohort (P<0.001) studies, in men (P<0.001), and for current smokers (P<0.042). Heterogeneity was absent for case-control studies and males and moderate for cohort studies and smokers. (Fabiani 2016) Contrary results were reported by some individual studies included in the Fabiani 2016 systematic review, including a 21% reduction in risk of lung cancer among women in the large prospective Nurses' Health Study, but no effect among men in the Health Professionals' Follow-up Study(Feskanich 2000) or the Zutphen study.(Arts 2001a)

Prostate cancer

No association was found between apple intake and the risk of prostate cancer when data from 2 case-control studies were pooled in a large systematic review and meta-analysis.(Fabiani 2016)

Renal cancer

High apple consumption (more than 94 g/day) was associated with reduced renal cancer risk in a population-based case-control study. The reduction was particularly strong for individuals who ate the most apples and for nonsmokers; no effect was observed in smokers.(Lindblad 1997)

Other cancers

One study compared 8,029 patients with cancer (oral, pharyngeal, esophageal, laryngeal, colorectal, breast, ovarian, or prostate cancer) with 6,629 patients without cancer. Consumption of 1 or more apples per day was inversely associated with the risk of cancer compared with consumption of less than 1 apple per day.(Gallus 2005)

In a 2017 systematic review and meta-analysis, pooled data from 16 cohort studies enrolling thousands of participants across numerous countries did not find any overall association between intake of apples (sometimes grouped with pears) and total cancer (ie, cancer risk, cancer deaths). Results from individual large cohorts that separated out apples as a subgroup were equivocal. The Calcium Intake Fracture Study (N=1,456 women; older than 70 years; 15-year follow-up) found a significant reduction in cancer deaths with apple intake of 39 g/day (RR=0.65; 95% CI, 0.45 to 0.95) and 154 g/day (RR=0.53; 95% CI, 0.29 to 0.97). In contrast, neither the Migrant Study (9,648 men; mean age, 58 years; 20.3-year follow-up) nor the Women's Health Study (N=38,408 women; age 45 years or older; 11.5-year follow-up) found a significant effect of apple intake on total cancer outcomes.(Aune 2017)

Cardiovascular disease

Multiple mechanisms for cardiovascular protection have been associated with apple antioxidant activity, along with apple fiber content effects.(Boyer 2004) Relevant mechanisms include decreasing lipid oxidation,(Kahle 2005, Mayer 2001, Pearson 1999) lowering cholesterol,(Aprikian 2001, Aprikian 2002, Leontowicz 2001, Leontowicz 2002, Leontowicz 2003) improving blood glucose and lipid profiles, reducing risk of type 2 diabetes, beneficial effects on obesity,(Boyer 2004) improving endothelial function and bioactivity of nitric oxide,(Hollands 2013) and clearing of uremic toxins via conjugation of certain polyphenols (ie, tyrosine, tryptophan) by gut microbiota.(Trost 2018)

Clinical data

In a 2017 systematic review and meta-analysis, pooled data from 16 cohort studies with thousands of participants in numerous countries found overall that high intake of apples was inversely associated with the risk of coronary heart disease (RR=0.85; 95% CI, 0.79 to 0.93), total stroke (RR=0.88; 95% CI, 0.81 to 0.96), subarachnoid hemorrhage (RR=0.56; 95% CI, 0.34 to 0.92), cardiovascular disease (RR=0.86; 95% CI, 0.8 to 0.93), and all-cause mortality (RR=0.8; 95% CI, 0.7 to 0.91) compared with low apple intake. Data regarding apples and pears were sometimes grouped because of similarity in nutrient profiles between the 2 fruits. Population sizes ranged from approximately 5,000 to 66,000, and follow-up duration ranged from 6 to 26 years. However, heterogeneity was low only for the coronary heart disease analysis. Individual large cohorts that evaluated apple and pear subgroups separately reported reduced risk of cardiovascular disease or all-cause mortality with high intake of apples; studies included the Finnish Mobile Health Examination Survey (total stroke and thrombosis for men, not women; all-cause mortality for men and women), the Calcium Intake Fracture Study (cancer deaths and all-cause mortality), and the Migrant Study (all-cause mortality in men). In contrast, the Nurses' Health Study, the Women's Health Study, the Calcium Intake Fracture Study, and the Migrant Study found no effects of apple intake on nonfatal myocardial infarction, coronary heart disease, cardiovascular disease, stroke deaths, cancer, and/or cancer deaths in women and/or men.(Aune 2017)

In nearly 35,000 postmenopausal women in an Iowa study, apple and wine consumption were inversely associated with coronary mortality.(Arts 2001b) No reduction in risk of death from coronary heart disease was observed in the Zutphen Study in elderly men, in whom apple intake contributed to approximately 10% of the total ingested flavonoids.(Hertog 1993) Among 160 healthy postmenopausal women randomized to dried apple (75 g/day) or dried plum (100 g/day) for 1 year in a single-blind controlled study, dried apple improved some lipids, atherogenic risk ratios, and oxidative stress markers compared with baseline at some, but not all, time points inconsistently throughout the year. Nonsignificant differences between groups were observed at 12 months.(Chai 2012)

In 1,456 women older than 70 years enrolled in a 5-year double-blind, randomized, controlled trial (Calcium Intake Fracture Outcome Study), effects of total and individual fruits (including apple) on abdominal aortic calcification were examined. Abdominal aortic calcification scores were significantly negatively associated with apple intake (P<0.01) but not with intake of other specific fruits (ie, pears, oranges, bananas) or with total fruit consumption. In contrast to intake of other fruits or total fruit intake, each standard deviation increase in apple intake (approximately half of a small apple [50 g/day]) was associated with approximately 25% lower odds of having severe disease in both age-adjusted (P=0.003) and multivariate-adjusted (P=0.009) models. There was no attenuation of this relationship after adjustment for total flavonoid, fiber, potassium, magnesium, vitamin C, or total vegetable or saturated fat intake (OR=0.7 [95% CI, 0.55 to 0.91]; P=0.008); the OR for severe abdominal aortic calcification in relation to apple intake was then stratified according to BMI, health status, and use of medications.(Bondonno 2016)

Acute increases in plasma and/or urinary nitrates and nitric oxide metabolites have been demonstrated in healthy adults after consumption of whole apples, whole apple puree, and flavanol-rich apple extract in some studies,(Bondonno 2014, Gasper 2014) but not others,(Bondonno 2018) or after consumption of only high-dose (140 mg) apple epicatechin extract in another.(Hollands 2013) Results regarding a correlation between plasma nitrate response and endothelial function have been equivocal.(Auclair 2010, Cicero 2017, Saarenhovi 2017) Although a change from baseline in flow-mediated dilatation (FMD) was noted after consumption of apple extract 330 mg/day (100 mg/day of epicatechin) in one randomized crossover study in patients with borderline hypertension or unmedicated mild hypertension, the change was not different than with placebo, either acutely or after 4 weeks of supplementation. Additionally, no differences were observed in nitrate-mediated dilatation, blood pressure, or biomarkers of vascular function.(Saarenhovi 2017) Similarly, a lack of effect on endothelial function with consumption of polyphenol-rich apples (1.43 g/day of polyphenols) versus polyphenol-poor apples (214 mg/day of polyphenols) for 4 weeks was noted in mildly hypercholesterolemic men in another small crossover study. Other biochemical parameters (ie, lipids, glucose, antioxidant status) were also not significantly affected.(Auclair 2010) In contrast, a double-blind, randomized, placebo-controlled study conducted in 62 overweight adults with suboptimal blood glucose levels revealed that 8 weeks of apple polyphenol extract (300 mg/day) significantly improved endothelial reactivity compared with placebo (P<0.05) and was inversely correlated with serum uric acid. Fasting blood glucose (FBG) and serum uric acid (SUA) also significantly improved with consumption of apple polyphenols compared with placebo (FBG, −10.4 mg/dL [P<0.001]; SUA, −0.3 mg/dL [P<0.025]).(Cicero 2017) Similarly, in a randomized, controlled crossover study of 30 adults with at least 1 risk factor for cardiovascular disease, consumption of high-polyphenol apples (306 mg/day total phenols [apple plus skin]) significantly improved adjusted mean percent FMD acutely (2 hours) as well as after 4 weeks compared with low-polyphenol apple ingestion (92 mg/day total phenols [apple flesh only]). At 4 weeks, no difference was observed between high- and low-polyphenol apple consumption in peak FMD, weight, blood pressure, arterial stiffness, plasma or salivary nitrates/nitrites, plasma heme oxygenase-1, bilirubin, plasma glucose, lipids, urinary creatinine, potassium, sodium, or the systemic oxidative stress biomarker F2-isoprostane.(Bondonno 2018)

In a study evaluating the effects of Annurca apple polyphenols on intermittent claudication in peripheral artery disease, comparisons to baseline showed improvement for patients receiving apple polyphenol extract (2,000 mg/day for 24 weeks) versus those receiving placebo. Specifically, walking autonomy improved by 69%, ankle-brachial index by 25%, and acceleration time by 3.6%; the placebo group did not experience such changes. No between-group comparisons were reported.(Tenore 2019b)

Significant improvements have also been noted in platelet reactivity of healthy adults, both acutely (2, 6, and 24 hours after treatment) and after 2 weeks of daily consumption of low- and high-flavanol apple puree (25 and 100 mg of epicatechin, respectively), with one study showing no significant difference in acute response between low-flavanol apple puree and aspirin (positive control). It should be noted that while low-flavanol puree and aspirin both significantly attenuated platelet reactivity at 2 weeks compared with baseline (P=0.0018 for each), high-flavanol apple puree resulted in a significant increase in some platelet reactivity biomarkers. Low-flavanol puree also produced a small but statistically significant decrease in mean triglycerides (1.3 mmol/L on day 15 compared with 1.1 mmol/L on day 29; P=0.002). No significant differences were observed in plasma lipids, C-reactive protein, or serum endothelial-1.(Gasper 2014)

Cognitive function/mood

Clinical data

In an open-label pilot study in elderly patients (mean age, 82 years) with moderate- to late-stage Alzheimer disease (N=21), no changes in cognitive scores were observed after consumption of apple juice for 1 month. In contrast, mood and behavior significantly improved. Compared with baseline, the mean behavior score improved by 3.5 points (P<0.001), with major improvement specifically in anxiety, apathy, agitation, depression, and delusion. Results were not correlated with age.(Remington 2010)

In 30 healthy volunteers (mean age, 47 years) enrolled in a randomized, controlled crossover trial, consumption of high-flavonoid apple (apple flesh plus skin), spinach, and apple plus spinach did not produce any differences in cognitive function, composite domain scores, or mood scores compared with the low-flavonoid control (apple flesh). The variety of apple used in the study was Pink Lady.(Bondonno 2014) Similarly in another small randomized crossover study, no improvement was seen in cognitive flexibility, executive function, verbal or visual memory, or reaction time compared with baseline in 20 healthy young women (and 1 male) who consumed 1 serving of dried apples. In contrast, psychomotor speed test scores were improved compared with baseline.(Sansone 2018)

Dental plaque

Clinical data

In 20 young dental students, chewing an apple lowered bacterial viability compared with baseline but not the plaque index (as assessed macroscopically by use of erythrosine stain). Results were better with manual tooth brushing with sterile water compared with apple chewing. The authors noted a limitation of the erythrosine stain that could have reflected a biofilm from the apple and/or staining of salivary proteins released by apple chewing and not necessarily reflecting plaque proteins.(Rubido 2018)

Diabetes and glucose metabolism

Specific polyphenols as well as the low glucose and high fructose:glucose ratio of dried apples appear to contribute to a low postprandial glycemic response.(Trost 2018, Wruss 2015, Zhu 2018)

Clinical data

A 2013 meta-analysis of 3 large cohort studies investigated the effects of fruit consumption on the risk of type 2 diabetes; data were collected for more than 35 years on almost 300,000 patients from the Nurses' Health Study, Nurses' Health Study II, and Health Professionals Follow-up Study (3,464,641 person-years of follow-up).

Overall, total whole fruit consumption was weakly associated with a reduced risk of type 2 diabetes (hazard ratio [HR]=0.98; 95% CI, 0.97 to 0.99) and when adjusted for age, the reduction in risk was significant for each individual whole fruit in each cohort (P<0.001). When at least 5 servings per week of apples and/or pears (grouped due to comparable nutrient profiles) were consumed, an inverse linear trend was observed for both age-adjusted and multivariate-adjusted analyses, with an HR of 0.61 (95% CI, 0.55 to 0.67) and 0.72 (95% CI, 0.64 to 0.8), respectively. Fruit juice consumption was associated with an increased risk of diabetes; however, mean risk decreased 7% when 3 servings per week of fruit juice were replaced with total whole fruits, decreased 14% when replaced with apples and pears, and decreased 33% when replaced with blueberries.(Muraki 2013)

In a double-blind, randomized, controlled trial of 65 Japanese adults with high-normal and borderline-type glycemia, supplementation with apple polyphenol extract 600 mg once daily for 12 weeks significantly reduced mean increase in plasma glucose at 30 minutes following a 75 g oral glucose tolerance test compared with placebo (164 vs 194.7 mg/dL, respectively; P<0.05). This effect was not observed in participants with normal plasma glucose levels. No significant differences were observed in glucose AUC, insulin sensitivity, lipid parameters, or inflammatory cytokines.(Shoji 2017) In a study from Brazil, hypercholesterolemic overweight women consuming apples or pears 3 times daily had a lower blood glucose level compared with women consuming oat cookies.(Conceição de Oliviera 2003) In overweight adults with suboptimal blood glucose, FBG and SUA significantly improved with consumption of apple polyphenol extract (300 mg/day for 8 weeks) compared with placebo (FBG, −10.4 mg/dL [P<0.001]; SUA, −0.3 mg/dL [P<0.025]).(Cicero 2017)

In 25 healthy volunteers (men and postmenopausal women), consumption of apple polyphenol extract alone and in combination with blackcurrant anthocyanins significantly lowered early postprandial plasma glucose, insulin, and C-peptide compared with placebo control. The combination had a stronger effect than the apple extract alone. Study participants consumed each test drink prior to a high-carbohydrate test meal. The estimated corresponding physiological dose in humans was 600 mg of apple polyphenols (900 mg of apple extract).(Castro-Acosta 2017) In a small randomized, crossover trial in 11 healthy young students, consumption of dried apples resulted in a significantly lower increase in peak postprandial plasma glucose at 30 minutes from baseline (+1.8 mmol/L) compared with all other dried fruit (eg, raisins, apricot, jujubes), rice, and glucose (control) test meals (P=0.027). Similar results occurred within 240 minutes of consumption for dried apples alone (+2.1 mmol/L; P<0.05) or when added to rice (+2.5 mmol/L; P<0.05), with incremental increases in peak postprandial glucose ranging from 2.6 to 3.9 mmol/L for each of the other individual samples and from 3.2 to 3.5 mmol/L when each was combined with rice. However, no significant difference was found between dried apples plus rice and almonds plus rice (+2.7 mmol/L). A significant direct correlation was found between total glucose content of the test meal and postprandial peak glucose AUC. In contrast, a very strong inverse correlation was observed for the ratio of total fructose to total glucose, such that the test meal with the highest fructose:glucose content ratio (ie, dried apples) led to lower postprandial glucose excursion. No significant associations were found between glycemic response and total carbohydrate, fiber, pectin, or organic acid content, or antioxidant capacity.(Zhu 2018) In another small randomized crossover study, acute plasma glucose and insulin concentrations were better in 20 healthy young women (and 1 male) who consumed 1 serving of dried apples compared with consumption of a muffin.(Sansone 2018) Similarly, when data from 51 of 73 young healthy adults randomly assigned to test (apples or apple juice) or control groups were evaluated in a crossover study, an acute increase in blood glucose was observed 30 minutes after consumption of 1 apple (205 g), 2 apples (410 g), and 170 mL and 340 mL of 100% apple juice. Plasma glucose levels predominantly returned to baseline 60 minutes after ingestion of test intervention.(White 2018) In another study, dose-dependent decreases were noted in postprandial glucose in subjects consuming a polyphenol-rich apple drink following a high-carbohydrate meal; however, the total glucose AUC and early glucose responses were not significantly reduced.(Prpa 2020).

GI diseases

Acute gastroenteritis

Clinical data

Apple juice offered benefit over electrolyte solution for rehydration and recovery in a single-blind, randomized, noninferiority trial of 647 children 6 months to 5 years of age with acute gastroenteritis and minimal dehydration. Administration of half-strength apple juice followed by the patient's preferred fluids resulted in significantly fewer treatment failures than in those assigned exclusively to electrolyte maintenance solution (16.7% vs 25%, respectively; P<0.001). The benefit was most notable in children at least 2 years of age, with the improvement in hospitalization rates being the predominant difference among the composite measures (0.9% vs 2.8%, respectively). The apple juice group also required significantly fewer intravenous (IV) rehydration solutions (difference, −5.9%) at the index visit.(Freedman 2016)

Cholera

Animal data

Animal studies reported that crude extract of immature apples inhibited the enzymatic activities of, and the fluid accumulation induced by, the cholera toxin in a dose-dependent manner. It is likely that polymerized catechins are responsible for this action.(Saito 2002)

Inflammatory bowel disease

Animal data

A study in mice with chemically induced colitis showed beneficial anti-inflammatory and immunomodulatory effects of apple procyanidins on intestinal epithelial cells and intraepithelial lymphocytes, suggesting that apples may be an effective preventive agent for inflammatory bowel disease.(Yoshioka 2008) Another study showed that administration of apples rich in polyphenols ameliorates colon inflammation in rats developing spontaneous inflammatory bowel disease.(Castagnini 2009)

Hair growth

In vitro data

In vitro data support increases in keratin expression and high-weight molecular cytokeratin isoforms, with no interference with keratinocyte viability.(Tenore 2018)

Clinical data

Data from a double-blind, randomized, placebo-controlled trial suggest that Annurca apple extract administered in gastric-resistant capsules twice daily for 8 weeks increases hair growth as well as hair weight and keratin content in males and females with evidence of pattern baldness. Statistical analysis of data from 5 of the 168 participants showed more than a 100% increase from baseline for hair growth.(Tenore 2018)

Hypercholesterolemia

Hypocholesterolemic effects vary among apple cultivars and are positively correlated with polyphenol amount; Annurca and Granny Smith were more beneficial than Fuji and Golden Delicious varieties.(Tenore 2017, Tenore 2019a) The different types of pectin also appear to play a role in the ability to lower cholesterol, with the more highly esterified pectin (degree of esterification greater than 50%) forming a gel with high sugar content at low pH and providing a more pronounced effect than pectin of a lower degree of esterification.(Brouns 2012) It has also been demonstrated that lactobacilli fermentation can further these effects by increasing availability of free polyphenols by more than 30%. The magnitude of changes was species- and time-dependent.(Tenore 2019a)

Clinical data

Apples have been shown to lower cholesterol in humans.(Boyer 2004) In a randomized, double-blind, placebo-controlled study in moderately obese men and women (BMI ranging from 23 to 30), 12-week intake of polyphenols from apples and hop bract (600 mg/day) decreased total cholesterol and low-density lipoprotein (LDL) cholesterol levels. Effects of apple-containing capsules were more marked than with hop bract, suggesting apple polyphenols regulate fat metabolism in healthy subjects with high BMIs.(Nagasako-Akazome 2007) Similarly, cultivars of 5 fresh apples improved lipid parameters in a single-blind, randomized, placebo-controlled trial conducted in 250 adults with mild hypercholesterolemia. Patients consumed 200 g of apple (1 or 2 depending on the size) daily for 8 weeks, which led to improvements in total cholesterol, LDL, and high-density lipoprotein (HDL) within the first month of the study. Hypocholesterolemic effects were positively correlated to the polyphenol amounts in each cultivar, which in decreasing order were as follows: Annurca, Granny Smith, Red Delicious, Fuji, Golden Delicious. Decreases in total cholesterol ranged from −8.3% to −1.2%, while LDL reductions ranged from −14.5% to −2.6%. Improvements were also observed in HDL and ranged from +14% to +1.5%. In contrast, plasma glucose and triglycerides increased by an average of +13.1% and +12.7%, respectively.(Tenore 2017)

Lactofermented apple puree improved HDL and antioxidant parameters compared with unfermented apple puree in 90 patients with increased cardiovascular risk, specifically borderline high cholesterol and triglycerides. Patients were randomized to either lactofermented or unfermented apple puree (125 g/day) or a Lactobacillus rhamnosus capsule, which were given with a meal for 8 weeks. The 3 products were matched for lactobacilli content (approximately 3x108 CFU). Fermented apple puree produced the greatest improvement in mean HDL, with a 61.8% increase during the 8 weeks (range, 35.4 to 57.3 mg/dL) compared with the unfermented puree (+48.4%) and the lactobacilli capsule (+17.7%). Significant results were achieved after the first 4 weeks and were still significant 4 weeks after the intervention period. Similar results were observed for antioxidant status. Changes in total cholesterol, LDL, glucose, and triglycerides were not significant.(Tenore 2019a)

Neurodegeneration and aging

Animal data

Experimental studies in rat and mouse models demonstrated that impairment of brain function during aging could be prevented by an increase in apple consumption.(Chan 2006a, Chan 2006b, Chan 2009, Ko 2005, Rogers 2004, Tchantchou 2005, Viggiano 2006)

Clinical data

In an open-label pilot study (N=21), consumption of apple juice for 1 month significantly improved mood and behavior in elderly patients (mean age, 82 years) with moderate- to late-stage Alzheimer disease. Compared with baseline, the mean behavior score improved 3.5 points (P<0.001), with major improvement observed specifically in anxiety, apathy, agitation, depression, and delusion. Results were not correlated with age. In contrast, no changes were observed in cognitive scores or activities of daily living.(Remington 2010)

A study in 15 elderly subjects consuming an apple a day for 1 month revealed lower oxidant levels and higher antioxidant potential after the study period compared with prestudy levels. It was concluded that reduced peroxidation processes owing to consumption of apple may play a part in some of the beneficial effects observed in elderly subjects.(Avci 2007)

Niacin-induced flushing

Clinical data

In a double-blind, randomized, placebo-controlled trial (N=100), apple pectin provided protection similar to aspirin, with both significantly reducing the duration of flushing when given 30 minutes prior to a niacin 1,000 mg dose. Consumption of apple pectin 2,000 mg or non–enteric-coated aspirin 325 mg led to a significant reduction in duration of flushing (duration, 25 minutes and 20 minutes [P=0.038 and P=0.024], respectively) compared with the duration in the placebo group (60 minutes). In contrast, administration of aspirin plus apple pectin resulted in a 45-minute flush duration. Other numerical improvements in the apple pectin group included lower time to flush and reduced maximum severity, but differences from placebo were not statistically significant.(Moriarty 2013)

Obesity

Animal data

A study in rats compared the effects of dietary apple polyphenol (diets containing 5% or 0.5% of apple polyphenols) with control. After a 3-week experimental period, adipose tissue weights in the 5% group were lower than those in the control group. Pathological examination suggested the existence of proliferating pre-adipocytes only in the control group. The authors concluded that dietary apple polyphenol had an antiadipogenic effect.(Nakazato 2006)

Clinical data

Various clinical studies have illustrated that apple polyphenols may regulate fat metabolism.(Nagasako-Akazome 2007) In a study from Brazil, hypercholesterolemic nonsmoking women were randomized to consume apple, pear, or oat cookies 3 times daily for 12 weeks. Participants consuming either fruit had weight loss, whereas those ingesting oat cookies did not.(Conceição de Oliviera 2003) In a blinded, randomized, controlled study (N=68), obese German males who consumed 750 mL/day of polyphenol-rich cloudy apple juice for 4 weeks experienced significant reductions in body fat percentage compared with those in the control beverage group (−1% vs −0.2%; P=0.001). The control beverage was matched for sugar, mineral, acid, and vitamin C composition to the cloudy apple juice. A significant genotype-based association with body fat mass reduction was observed: Carriers of the interleukin 6-174 C/C variant had a significant reduction in body fat after 4 weeks of polyphenol-rich cloudy apple juice, compared with carriers of the G-allele (G/C, G/G) variants. No significant changes were observed in adipokines or biomarkers for systemic or vascular inflammation in the treatment group.(Barth 2012)

In a crossover study, data from 51 of 73 young healthy adults randomly assigned to a fructose-matched intervention of Royal Gala apples, 100% apple juice, or fructose or glucose control beverage revealed greater acute satiety 30 minutes after ingestion of whole apples compared with apple juice. No differences in satiety scores were noted between the fructose and glucose control beverages.(White 2018)

Osteoporosis

Clinical data

In a randomized, comparative trial conducted in 100 postmenopausal women, consumption of either dried apple (75 mg/day) or dried plum (100 mg/day) for 1 year increased total body bone mineral density compared with baseline. Effects were similar between groups, except for the ulna and spine, for which dried apple provided less bone-protective effects. Results were supported by serum biomarkers. Overall compliance averaged 82%.(Hooshmand 2011)

Uric acid metabolism

Clinical data

Effects of apples and apple juice on acute plasma uric acid concentration were evaluated in a randomized controlled crossover trial; data from 51 of the 73 young healthy adults randomly assigned to test (apple or apple juice) or control (fructose beverage and glucose beverage) groups were analyzed. When test interventions were matched for fructose content, an acute increase in plasma uric acid concentration was determined to be the result of fructose, regardless of the source, and not glucose consumption. Consumption of Royal Gala apples, 100% apple juice, or a fructose control beverage within a 10-minute period increased plasma uric acid concentrations at 30 minutes postingestion, with no difference between the apple interventions and fructose control. Doubling the serving size of fructose-based intervention almost doubled uric acid levels. In contrast, the glucose control produced a small decrease in uric acid levels.(White 2018)

Apples side effects

Research reveals little or no information regarding adverse reactions with the use of apples, except for allergy. Approximately 2% of the northern and central European population is allergic to apples.(Kootstra 2007) Oral allergy syndrome is a common presentation(Chang 2005, Ozcelik 2006); however, contact urticaria has also been reported.(Chang 2005) Two cases of apple-dependent, exercise-induced anaphylaxis were reported.(Sánchez-Morillas 2003)

There is evidence that allergenic potential is dependent on the apple cultivar, with some varieties being less allergenic.(Kootstra 2007) One study revealed approximately 100-fold differences among cultivars in lipid proteins implicated in severe allergic reactions to fruits.(Sancho 2008) Cross-sensitivity among the apple fruit and other members of the Rosaceae family has been demonstrated.(Rodriguez 2000)

Before taking Apples

Apples have GRAS status when used as food. Avoid consumption of amounts greater than those typically found in food, because safety and efficacy are unproven.(FDA 2019)

How to use Apples

Limited robust clinical trials provide unequivocal data to support dosing for specific conditions.

Abdominal aortic calcification

In age- and multivariable-adjusted models, each standard deviation increase in apple intake (approximately half of a small apple [50 g/day]) reduced risk of severe disease in a 5-year study of elderly women.(Bondonno 2016)

Obesity and associated comorbidities

750 mL/day of polyphenol-rich cloudy apple juice for 4 weeks was evaluated in a study of obese men.(Barth 2012)

Diabetes mellitus type 2 risk

Replacing each 3 servings/week of fruit juice consumption with the same amount of total or individual whole fruits (including whole apple) was associated with lower type 2 diabetes risk; processed fruit juice consumption was associated with an increased risk.(Muraki 2013) Apple polyphenol extract 600 mg once daily for 12 weeks was used in adults with high-normal and borderline-type hyperglycemia to improve impaired glucose tolerance.(Shoji 2017)

Dyslipidemia

Consumption of 200 g of apple (1 or 2 apples depending on the size) daily for 8 weeks was evaluated in a study of mildly hypercholesterolemic healthy subjects; antidyslipidemic effects were correlated to the polyphenol amounts in each cultivar, which in decreasing order were as follows: Annurca, Granny Smith, Red Delicious, Fuji, Golden Delicious.(Tenore 2017) In another study, lactofermented Annurca apple puree 125 g/day for 8 weeks was evaluated in individuals with cardiovascular disease risk factors.(Tenore 2019a)

Gastroenteritis

Half-strength apple juice followed by preferred fluids was administered in children 6 months to 5 years of age with mild gastroenteritis.(Freedman 2016)

Niacin-induced flushing

2,000 mg of apple pectin was evaluated as pretreatment to niacin dosing, and produced equivalent effects to 325 mg of non–enteric-coated aspirin.(Moriarty 2013)

Osteoporosis risk in postmenopausal women

Dried apple 75 mg/day for 1 year was evaluated for effects on bone health and fracture risk.(Hooshmand 2011)

Pulmonary function

A study of middle-aged men evaluated associations between consumption of apple (at least 5 apples per week) and lung function.(Butland 2000)

Polyphenol bioavailability, metabolism, urinary excretion, and metabolite composition can vary significantly among individuals due to differences in personal genotypes and gut microbiota profiles, as well as the form of apple consumed (ie, whole apple, juice, extract). Mean Cmax, area under the curve (AUC0-24), predicted absorption, and urinary yield of apple polyphenols were all significantly lower with apple puree versus extract; time to maximum concentration was significantly longer with apple puree versus extract. In plasma, polyphenols occur in both the free and protein-bound form (ie, albumin). After consuming 500 mL of organic, unfiltered apple juice containing 1,080 mg of polyphenols, an immediate increase in free plasma polyphenols occurs in the first hour. When comparing the average concentration of free polyphenol compounds after 6 hours to the overnight fast samples, a 19% increase in the total content could be observed. The average phenolic excretion is 14.8 mg (range, 0.6 to 93.4 mg), which occurs approximately 3 to 4 hours after consumption. Based on elimination of polyphenols, individuals may be categorized as "fast" (maximum excretion after 1 hour after ingestion), "average" (maximum excretion 6 hours after excretion), "slow" (maximum excretion 8 hours after ingestion), "low" (no significant difference compared with baseline), or "multiple" (2 time-points of maximum excretion [eg, 1 hour and 6 to 8 hours postconsumption]) excreters. Females tend to have significantly lower mean total phenolic concentrations than males in urine (700 mg/L vs 900 mg/L, respectively; P<0.001) and plasma (P<0.01); however, changes in levels over time were similar between genders.(Hollands 2013, Trost 2018, Wruss 2015)

Compounds metabolized in the upper gut independent of the gut microbiota typically reach maximum plasma and/or urine concentration within 5 hours of consumption, whereas the same nutrikinetic values for catabolites that result from gut microbiota biosynthesis are more delayed and Cmax may not be reached until after 24 hours, if at all. Microbiota bacterial conjugation of certain apple polyphenols (ie, tryptophan, tyrosine) may be associated with clearance of toxins, specifically some uremic toxins that have been associated with cardiovascular disease risk.(Trost 2018)

Warnings

Apples have GRAS status when used as food.

One study in rats addressed toxicology and safety of a polyphenol-rich extract from unripe apples containing high levels of oligomeric procyanidins (64%), flavan-3-ols (12%), flavonoids (7%), and nonflavonoids (18%). At a dose of 2,000 mg/kg body weight, no signs of toxicity were observed in acute and subchronic toxicity tests.(Shoji 2004)

Because of their hydrogen cyanide content, apple seeds should not be ingested in large quantities. A small number of seeds may be ingested without symptoms.(Lampe 1985) Large amounts of seeds have the potential for toxicity. There is one case report of death from cyanide poisoning in a man who ingested a cupful of apple seeds.(Duke 1985) Because cyanogenic glycoside must be hydrolyzed in the stomach in order to release cyanide, several hours may elapse before symptoms of poisoning occur.(Lampe 1985)

What other drugs will affect Apples

Some studies have reported insignificant pharmacokinetic drug interactions with natural products. Limited information as well as potentially high interpatient variability in clinical response warrants cautious interpretation and/or application of these data in practice.

Apple juice can potentially decrease the absorption of certain drugs via inhibition of OATPs, which are involved in drug uptake in the gut, liver, and kidney.(Bailey 2001, Dresser 2002, Yu 2017)

In healthy adults, apple puree/applesauce used as a vehicle for drug delivery did not affect the time-concentration profiles of nilotinib or edoxaban and its M-4 metabolite in 2 separate studies. All participants in one study were White, and 50% were White and 43.3% were Black in the other study.(Duchin 2018, Yin 2011) Recommendations for elvitegravir include administration with food to maximize plasma levels; it is also usually given with the pharmacokinetic booster cobicistat. Administration of elvitegravir with apple juice resulted in much lower time-concentration profiles of elvitegravir in healthy, HIV-negative Japanese males compared with milk or a protein-rich drink. In contrast, systemic exposure of cobicistat was unaffected.(Yonemura 2018)

A systematic review of preclinical and clinical findings noted clinically important reduced drug exposure (at least 20%) for aliskiren, atenolol, fexofenadine, and nizatidine with coadministration of apple juice given as either a single dose or as multiple doses over 3 hours to 5 days. Overall, reductions in AUC and Cmax for the various drugs ranged from 27.2% to 83.5% and from 44.2% to 87.3%, respectively. Reductions of 80% to 87% in both AUC and Cmax were observed for atenolol and fexofenadine, and a reduction of 83% in Cmax was observed for aliskiren.(Yu 2017) Separating administration times might not prevent these interactions.

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