T Enomoto, et al

Original Article

Clinical Effects of Apple Polyphenols

on Persistent Allergic Rhinitis:
A Randomized Double-Blind Placebo-
Controlled Parallel Arm Study
T Enomoto,1 Y Nagasako-Akazome,2 T Kanda, 2 M Ikeda,2 Y Dake 1
1
Department of Otolaryngology, Japanese Red Cross Society, Wakayama Medical Center, Wakayama, Japan
2
Fundamental Research Laboratory, Asahi Breweries Ltd, Moriya-shi Ibaraki, Japan

Abstract. Background: We often encounter persistent allergic rhinitis due to house dust mites in the practice of
otolaryngology, and its prevalence in Japan is high (18.7 %). Persistent allergic rhinitis is usually treated with
antihistamines and local steroids, but they often cause adverse effects such as sedation and drowsiness. Polyphenols
derived from apples have been reported to suppress histamine release from rat cells, reduce auricular swelling in
allergic mice, and alleviate skin inflammation in atopic patients. These effects suggest that apple polyphenols are
effective for the treatment of various allergic disorders, but the results of their clinical use have not been reported.
Objective: To assess the effect of drinks containing apple polyphenols on clinical symptoms of persistent allergic
rhinitis.
Methods: Thirty-three patients aged 15 to 65 years with moderate or severe persistent allergic rhinitis in whom the
symptoms persisted for 3 years or longer were treated without apple polyphenols (control group), with a low dose
of apple polyphenols, or with a high dose of apple polyphenols, and changes in the clinical symptoms were
examined.
Results: Significant improvements were observed in sneezing attacks (P < .05) and nasal discharge (P < .01) in the
high-dose group and in sneezing attacks (P < .05) in the low-dose group. Compared with the control group, an
improvement was observed in sneezing attacks and nasal discharge in many patients of the polyphenol-treated
groups. In terms of intranasal findings, a significant improvement was observed in swelling of the nasal turbinate
in the low-dose group (P < .05). The percentage of patients who showed an improvement in swelling of the nasal
turbinate was higher in the polyphenol-treated groups.
Conclusions: We conclude that apple polyphenols are effective in alleviating symptoms of persistent allergic
rhinitis.

Key words: Apple polyphenols. Nasal allergy. Sneezing attack. Nasal discharge. Human clinical trial.

Resumen. Antecedentes: En las consultas de otolaringología, a menudo nos encontramos con rinitis alérgica
persistente debida a ácaros de polvo doméstico. Su prevalencia en Japón es alta (del 18,7 %). Normalmente la
rinitis alérgica se trata con antihistamínicos y esteroides locales aunque éstos pueden conllevar efectos secundarios
tales como sedación y somnolencia. Los polifenoles derivados de la manzana han demostrado suprimir la histamina
liberada por células de ratas, reducir el edema en la zona auricular de ratones alérgicos y aliviar inflamaciones
cutáneas en pacientes atópicos. Estos efectos sugieren que los polifenoles de la manzana son efectivos en el
tratamiento de varios trastornos alérgicos, pero todavía no se han confirmado sus resultados en uso clínico.
Objetivo: Evaluar el efecto de bebidas que contienen polifenoles de manzana en síntomas clínicos de rinitis
alérgica persistente.
Métodos: Se trataron 33 pacientes entre 15 y 65 años con rinitis alérgica persistente moderada o severa cuyos
síntomas persistieron durante al menos 3 años sin polifenoles de manzana (grupo de control), con una dosis baja
de polifenoles de manzana, o con una dosis elevada de polifenoles de manzana; finalmente se examinaron los
cambios en los síntomas clínicos.
Resultados: Se observaron mejorías significativas en las salvas de estornudos (P < 0,05) y rinorrea (P < 0,01) en el

J Investig Allergol Clin Immunol 2006; Vol. 16(5): 283-289 © 2006 Esmon Publicidad
 Effects of Apple Polyphenols on Persistent Allergic Rhinitis 284

grupo de dosis alta así como en salvas de estornudos (P < 0,05) en el grupo de dosis baja. En comparación con el
grupo de control, se observó mejoría en salvas de estornudos y rinorrea en muchos pacientes de los grupos tratados
con polifenoles. En cuanto a los hallazgos intranasales, se observaron mejorías significativas en el edema de
cornetes nasales en el grupo de dosis baja (P < 0,05). El porcentaje de pacientes con mejorías en el edema de
cornetes nasales fue mayor en el grupo tratado con polifenoles.
Conclusiones: Concluimos que los polifenoles de manzana son efectivos para aliviar los síntomas de rinitis alérgica
persistente.

Palabras clave: Polifenoles de manzana. Alergia nasal. Salvas de estornudos. Descarga nasal. Prueba clínica humana.

Introduction
n=2~15
The most frequent allergen in persistent allergic
rhinitis is considered to be the house dust mite, and its
OH
primary pathogenic mechanism is reported to be type I
allergic reaction triggered by an interaction between an 8
HO 0 OH
allergen and specific IgE antibodies on mast cells. The
prevalence of the disease in Japan is reported to be high
at 18.7 % [1]. The disease is usually treated with
antihistamines and local corticosteroids, but long-term 4 OH
administration is required and adverse effects of the drugs
OH
are often experienced. n
There have been many reports of antiallergic activities
displayed by polyphenols, including those of green tea,
Figure 2. Chemical structure of procyanidins.
persimmon leaf, ten-cha, and perilla [2-5]. However, the
active components have not been identified. Apple
polyphenols have been registered among Japanese also been reported to inhibit histamine release from rat
Standard Food Additives as antioxidants due to their cells [12], suppress auricular swelling in allergic mice [13],
strong antioxidant activity. Moreover, they have and alleviate skin inflammation in atopic patients [14].
physiologic functions such as regulation of the Apple polyphenols are extracted and purified from
metabolism of oxidized cholesterols in rats [6-8] and of unripe apples and consist primarily of procyanidins
cholesterols in humans [9]. They also display anticaries (Figures 1 and 2), and a purified concentrated procyanidin
activities [10] and have been reported to be safe on long- fraction has been confirmed to have higher activity in
term administration based on mutagenicity tests and a tests using rat cells [12]. Stabilization of mast cells and
90-day oral administration test [11]. Polyphenols have basophils [12] and the control of immunotolerance [15]
have been suggested as possible mechanisms underlying
the action of polyphenols. These findings suggest that
allergic symptoms may be alleviated by ingestion of apple
polyphenols. However, as regular intake of an effective
Others dose of apple polyphenols is difficult in an ordinary diet,
5% they must be processed into forms that can be ingested
Flavinoids
8% readily, for example, by adding them to drinks. In this
study, we prepared drinks containing apple polyphenols
Catechins and evaluated their effects on clinical symptoms of
9% persistent allergic rhinitis.

Procyanidins
Phenol carboxylic 52 % Materials and Methods
acids
26 % Subjects
The study involved 33 patients with persistent allergic
rhinitis due to house dust mite allergy in whom moderate
or severe allergic symptoms had been present for at least
3 years. Patients were recruited on the basis of a clinical
history of allergic rhinitis and at least 2 of the following
Figure 1. Composition of apple polyphenols. criteria: positive skin tests or demonstration of IgE to

© 2006 Esmon Publicidad J Investig Allergol Clin Immunol 2006; Vol. 16(5): 283-289
285 T Enomoto, et al

-1 0 4
(Week)
Ingestion period of study
product

Clinical examination
(blood and urine sampling) • •

Figure 3. Test schedule.

house dust mites, eosinophils in nasal discharge, and dose, and high-dose groups to examine time of onset and
positive reaction on nasal challenge. Those individuals dose-dependence of the effect of apple polyphenols.
who had undergone specific immunotherapy in the 4 Applephenon (Asahi Food and Healthcare Ltd, Tokyo,
weeks prior to recruitment were excluded from the study. Japan) was used to prepare drinks with a polyphenol
The other exclusion criteria were the presence of other content of 50 mg per bottle for the low-dose group and
nasal complications, the use of drugs that might affect 200 mg per bottle for the high-dose group. A sham drink
the efficacy evaluation (antihistamines, antiallergic drugs, that did not contain apple polyphenols was prepared for
corticosteroids, etc), multiple sensitization that might the control group. The 3 drinks were made
affect the study, and pregnancy or lactation in women. If indistinguishable in taste or appearance, bottled, and
the use of drugs was unavoidable during the study, second- sealed with caps on which only code numbers were
generation antihistamines were used and the drug names, printed. The study was performed according to the
periods of use, and doses were recorded in the nasal schedule shown in Figure 3, and the test drinks were taken
allergy diaries. by the subjects at a dose of 1 bottle per day for 4 weeks.
All subjects were enrolled after giving informed consent Table 1 shows characteristics of the subjects in terms of
to participate in the study according to the process approved sex, age, severity of symptoms, presence or absence of
by the Ethics Committee, Seikokai Clinic, Tokyo. multiple sensitization, and presence or absence of
complications. Since the multiple sensitizations shown
by 7 subjects in each group were mild, the subjects were
Administration of Apple Polyphenols enrolled in the study. No significant difference was
observed between the groups. The nutritional contents of
The study followed a randomized, double-blind, the test drinks per 100 g were as follows: energy, 70 kcal;
placebo-controlled, parallel arm design with control, low- protein, 0 g; lipid, 0 g; and carbohydrates, 17 g.

Table 1. Subject Characteristics*

Group

Placebo Low High P

Number of subjects 11 11 11
Sex, male/female 2/9 6/5 1 / 10 < .05
Age, years 34.5 ± 3.73 32.5 ±3.41 38.5 ±2.77
Eosinophils in nasal discharge,
positive 11 11 11
Ratio of positive subjects on
nasal challenge 3/3 3/3 4/4
Severity of rhinitis
Mild 0 0 0 < .05
Moderate 11 8 11
Severe 0 3 0
Multiple sensitization 7 7 7
Other allergic disorders 0 1 4
*Data are shown as number or mean ± SEM.

J Investig Allergol Clin Immunol 2006; Vol. 16(5): 283-289 © 2006 Esmon Publicidad
 Effects of Apple Polyphenols on Persistent Allergic Rhinitis 286

Assessment of Nasal Scores However, as the compliance of this subject was 78.5%,
the subject was included in the analyses. There was no
Nasal symptoms (sneezing attacks, nasal discharge, problem in the compliance of the other subjects with the
and nasal obstruction) and signs (swelling of the nasal test regimen that might affect the analyses. Comparison
turbinate, color of inferior turbinate, watery secretion, and of the values in the high-dose and low-dose groups with
character of nasal discharge) were scored independently those in the control group using Dunnett’s test revealed
before and after treatment using a 4-point scale (for most no significant differences (Table 2).
variables, 0 indicates no symptom or sign; 1, mild; 2,
moderate; 3, severe; but in the case of the color of the
inferior turbinate, 0 corresponds to normal, 1 to slight Use of Other Medications
redness, 2 to red, and 3 to pale) based on the method
described by Okuda et al [16]. A medications score was Other medications were used by 8 subjects in the
used based on the guidelines of the Japanese Society of control group, 6 subjects in the low-dose group, and 5
Allergology [1]: use of a second-generation antihistamine subjects in the high-dose group. The periods over which
or a histamine-release suppressor was scored as 1, use of those medications were used were short in all subjects.
a local corticosteroid as 2, nasal application of a The use of medications was quantified using the
vasoconstrictor or an anticholinergic drug as 1, and use medication score and compared between the groups.
of an oral corticosteroid as 4. Comparison of the values in the high-dose and low-dose
groups with those in the control group by Kruskal-Wallis
test revealed no significant differences (Table 2).
Statistical Analysis
The Statview computer package (Abacus Concepts, Changes in Clinical Symptoms
NJ, USA) was used for all analyses. Data are expressed
as mean ± SEM. Changes in the values of each parameter The occurrence of sneezing attacks, nasal discharge,
from the beginning (week 0) to the end (week 4) of and nasal obstruction was scored according to Okuda et
administration were analyzed by Wilcoxon signed rank al [16] on the basis of the subject’s entries in the allergy
test or paired t test. Comparisons between groups were diaries, and the scores before and 4 weeks after the
performed by analysis of variance (Dunnett’s test or beginning of the intake were compared by Wilcoxon test
Kruskall-Wallis test) or Wilcoxon test. Statistical (Table 3). Significant improvements were observed in
significance was established at P < .05 or P < .01. sneezing attacks (P < .05) and nasal discharge (P < .01)
in the high-dose group and in sneezing attacks (P < .05)
in the low-dose group. However, there were no significant
Results differences between the high-dose or low-dose group and
the control group. Among the symptoms, improvements
Intake of Test Drinks in sneezing attacks and nasal discharge were greater in
the apple polyphenol-treated groups than in the control
The control group, low-dose group, and high-dose group. When intranasal findings were assessed, a
group each comprised 11 subjects. Table 2 shows the significant improvement (P < .05) was observed in
frequency of intake of the test drinks in the 33 subjects. swelling of the nasal turbinate in the low-dose group.
One subject in the high-dose group developed a rash on Consumption of apple polyphenols led to greater
the forehead 2 days after beginning intake of the test drink, improvements in sneezing attack, nasal discharge, and
and the symptom deteriorated with continued intake. swelling of inferior turbinate compared with placebo.

Table 2. Compliance and Medication Score*

Group

Placebo Low High P

Number of subjects 11 11 11
Compliance, % 99.7 ± 0.32 97.1 ± 1.58 96.8 ± 2.23 NS
Medication score 2.00 ± 1.62 0.55 ±0.37 0.91 ±0.48 NS
* Data are shown as number or mean ± SEM.
NS indicates not significant.

© 2006 Esmon Publicidad J Investig Allergol Clin Immunol 2006; Vol. 16(5): 283-289
287 T Enomoto, et al

Table 3. Effects of 4 Weeks Daily Intake of Apple Polyphenol Drinks *

Score
Nasal Symptom or Sign Group n P†
3 2 1 0
Sneezing attack Placebo Baseline 1 2 7 1 11
4 Weeks 0 1 7 3 11
Low Baseline 2 5 3 1 11 <. 05
4 Weeks 0 2 6 3 11
High Baseline 0 6 5 0 11 <. 05
4 Weeks 0 1 7 3 11

Nasal discharge Placebo Baseline 0 5 6 0 11

4 Weeks 0 0 9 2 11
Low Baseline 2 5 3 1 11
4 Weeks 0 3 6 2 11
High Baseline 0 8 3 0 11 < 0.1
4 Weeks 0 0 7 4 11

Nasal obstruction Placebo Baseline 0 5 4 2 11

4 Weeks 0 3 3 5 11
Low Baseline 1 5 4 1 11
4 Weeks 1 2 6 2 11
High Baseline 1 1 6 3 11
4 Weeks 0 1 6 4 11

Swelling of inferior turbinate Placebo Baseline 1 8 2 0 11

4 Weeks 2 6 2 1 11
Low Baseline 2 7 2 0 11 <. 05
4 Weeks 0 4 7 0 11
High Baseline 2 5 4 0 11
4 Weeks 1 6 4 0 11

Color of inferiorturbinate Placebo Baseline 4 2 5 0 11

4 Weeks 4 1 5 1 11
Low Baseline 5 0 6 0 11
4 Weeks 4 0 7 0 11
High Baseline 4 2 5 0 11
4 Weeks 3 2 6 0 11

Quantity of watery discharge Placebo Baseline 0 3 6 2 11

4 Weeks 0 0 7 4 11
Low Baseline 0 5 5 1 11
4 Weeks 0 1 7 3 11
High Baseline 0 4 5 2 11
4 Weeks 0 2 5 4 11

Character of nasal discharge Placebo Baseline 7 0 2 2 11

4 Weeks 6 0 1 4 11
Low Baseline 9 0 1 1 11
4 Weeks 6 0 2 3 11
High Baseline 7 0 2 2 11
4 Weeks 6 0 1 4 11
*Data are shown as number of subjects. Nasal symptoms and signs scored according to the method described by Okuda et al [16].
† Comparisons between baseline and 4 weeks by Wilcoxon test.

J Investig Allergol Clin Immunol 2006; Vol. 16(5): 283-289 © 2006 Esmon Publicidad
 Effects of Apple Polyphenols on Persistent Allergic Rhinitis 288

Overall Safety changed in the same model animals, the percentage

inhibition of auricular swelling was highest when the
Hematologic and serologic tests revealed significant interval was 2 to 4 hours but was very low when the
changes in hematocrit (increased by 0.9%) in the low-dose interval was 24 hours. These findings are consistent with
group and platelet count (increased by 1.8 ⴒ 104 cells/µL) a report showing that the blood concentration of
in the high-dose group. Biochemical tests showed that uric procyanidin in rats increased 1 to 4 hours after oral
acid concentration was significantly increased to 0.42 mg/dL administration of the procyanidin fraction of apple
in the high-dose group, while urinalysis showed that the polyphenols but decreased after 24 hours [18].
pH was increased by 0.64 in the low-dose group. All these Insight into the mechanism through which apple
changes were slight when considered within the standard polyphenols inhibit allergic reactions is provided by the
ranges and none posed clinical problems. observation that apple polyphenols and the procyanidin
In terms of adverse effects observed during the test- fraction prevent degranulation and histamine release by
drink intake period, 1 subject developed a rash on the inhibiting the increase in calcium concentration in
forehead, as mentioned. Other physical disorders included antigen-stimulated rat basophils (RBL-2H3 cells) [12].
soft stool (1 subject), diarrhea (2), constipation (2), Apple polyphenols are suggested to prevent degranulation
headache (1), cold symptoms (5), lower back pain (1), by promoting the stability of granulocytes and inhibiting
and mild dizziness (1). However, none of the conditions histamine release. In addition, apple polyphenols and their
were related to the intake of the test drink. procyanidin fraction may also suppress inflammation,
since they have been reported to have a dose-dependent
inhibitory effect on the activity of hyaluronidase, an
Discussion enzyme which is associated with inflammation and is
released by degranulation [12].
Persistent allergic rhinitis is a common disease in Apple polyphenols are made up of 50 % to 60 %
developed countries and its prevalence, which has been procyanidins, which are oligomers and polymers of
increasing in recent years, is reported to be high (18.7 %) catechins, along with low-molecular-weight polyphenols
in Japan [1]. The disease is primarily caused by house such as chlorogenic acid and catechins. However,
dust mites and is considered to occur via a type I allergic macromolecular procyanidins are not absorbed and are
reaction triggered by an interaction between the allergen considered to be mostly excreted [19]. The percentage of
and specific IgE antibodies on mast cells. The disease is γδ T cells in intestinal epithelial cells—an index of food
mainly treated with antihistamines and local allergy—was shown to decrease in a mouse model
corticosteroids, and long-term treatment is usually generated by continuous oral ingestion of ovalbumin, but
required. During treatment with antihistamines, adverse this decrease was prevented by administration of the
effects such as drowsiness due to suppression of the procyanidin fraction derived from apples [15]. In contrast,
central nervous system and thirst due to anticholinergic the decrease was not inhibited when catechins alone were
effects must not be overlooked. In particular, drowsiness administered. These results suggest that the apple-derived
reduces quality of life and work efficiency, and may procyanidin fraction may induce oral immunotolerance.
therefore lead to associated economic losses. The use of All of those findings strongly suggest that apple
corticosteroids, which have diverse pharmacological polyphenols are effective for the treatment of persistent
effects, must take into consideration the adverse reactions allergic rhinitis, which is a typical allergic disease. This study
that may appear with prolonged use [17]. In these was therefore performed to examine the effectiveness of
circumstances, screening familiar food items for apple polyphenols for the treatment of persistent allergic
antiallergic activities, developing them as functional rhinitis. Apple polyphenols were prepared as drinks to
foods, and using them to alleviate allergic symptoms may facilitate their regular daily intake in an effective dose. As a
be a therapeutic strategy worthy of consideration. result, a compliance of 79 % or higher could be achieved in
Polyphenols derived from unripe apples have been each group. In terms of clinical symptoms, sneezing attacks
reported to have antiallergic activities. In human atopic and nasal discharge showed significant improvements
dermatitis, itching, sleep disturbance, and peripheral (P < .05 and P < .01, respectively) after the treatment
eosinophil count have been reported to be significantly compared with the levels before the treatment in the high-
reduced in a group receiving oral apple polyphenols at dose group, and sneezing attacks also showed a significant
10 mg/kg for 8 weeks compared with a placebo-treated improvement in the low-dose group (P < .05). Moreover,
control group [14]. In animal experiments, swelling of improvements in sneezing attacks and nasal discharge were
the auricle was reported to be prevented by oral observed more frequently in the polyphenol-treated groups
administration of apple polyphenols in a murine model than in the control group. Assessment of intranasal findings
of type I allergy in which the auricle is thickened by the showed that swelling of the nasal turbinate was significantly
administration of anti-TNP IgE antibody-producing cells alleviated in the low-dose group (P < .05), and improvements
followed by the application of picryl chloride, a hapten in swelling of the nasal turbinate were observed in many
antigen, to the auricle [13]. In that study, when the interval subjects of the polyphenol-treated groups. The safety of
between the administration and antigenic stimulation was administering apple polyphenols was confirmed by various

© 2006 Esmon Publicidad J Investig Allergol Clin Immunol 2006; Vol. 16(5): 283-289
289 T Enomoto, et al

tests prior to the study [11], and adverse effects or abnormal 8. Akazome Y. Characteristics and physiological functions of
results on hematologic tests, serologic tests, or urinalysis polyphenols from apples. Biofactors. 2004; 22: 311-4.
were few and mild in this study. Therefore, the results of 9. Nagasako-Akazome Y, Kanda T, Ikeda M, Shimasaki H.
this pilot study suggest that apple polyphenols could be an Serum choresterol-lowering effect of apple polyphenols in
healthy subjects. J Oleo Sci. 2005; 54: 143-51.
excellent food component that contributes to the alleviation
10. Yanagida A, Kanda T, Tanabe M, Matsudaira F, Oliveira
of clinical symptoms of persistent allergic rhinitis and the CJG. Inhibitory effects of apple polyphenols and related
burdens of drug therapy. We will perform a clinical trial in a compounds on cariogenic factors of mutans streptococci. J
larger group to confirm the efficacy of apple polyphenols Agric Food Chem. 2000; 48: 5666-71.
for the treatment of rhinitis. In this study, we prepared apple 11. Shoji T, Akazome Y, Kanda T, Ikeda M. The toxicology and
polyphenols as drinks and achieved a high compliance. safety of apple polyphenol extract. Food Chem Toxicol.
Although a drink is a suitable dosage form to ensure 2004; 42: 959-67.
continuous intake of an effective dose of apple polyphenols, 12. Kanda T, Akiyama H, Yanagida A, Tanabe M, Goda Y,
other dosage forms that further improve the ease of intake Toyoda M, Teshima R, Saito Y. Inhibitory effects of apple
polyphenol on induced histamine release from RBL-2H3
may be developed by including them in other processed
cells and rat mast cells. Biosci Biotechnol Biochem. 1998;
foods. 62: 1284-9.
13. Akiyama H, Sakushima J, Taniuchi S, Kanda T, Yanagida
A, Kojima T, Teshima R, Kobayashi Y, Goda Y, Toyoda M.
Acknowledgments Antiallergic effect of apple polyphenols on the allergic model
mouse. Biol Pharm Bull. 2000; 23: 1370-3.
The authors are grateful to Drs. Kosaku Sakaguchi 14. Kojima T, Akiyama H, Sasai M, Taniuchi S, Goda Y, Toyoda
(Sakaguchi Otorhinolaryngology Clinic), Hiromu M, Kobayashi Y. Anti-allergic effect of apple polyphenol
Kakiuchi (Kakiuchi Otorhinolaryngology Clinic), Yutaka on patients with atopic dermatitis. Allergology International
2000; 49: 69-73.
Kato (Kato Clinic), and Yoshiaki Okuno (Okuno
15. Akiyama H, Sato Y, Watanabe T, Nagaoka M, Yoshioka Y,
Otorhinolaryngology Clinic), all of whom enthusiastically Shoji T, Kanda T, Yamada K, Totsuka M, Teshima R, Sawada
participated in the clinical assessment. J, Goda Y, Maitani T. Dietary unripe apple polyphenol
inhibits the development of food allergies in murine models.
FEBS Letters. 2005; 579: 4485-91.
References 16. Okuda M, Ishikawa T, Saito Y, Shimizu T, Baba D. A clinical
evaluation of N-5’ with perennial-type allergic rhinitis test
1. Baba K, Konno A, Takenaka H. Epidemiology. In: Okuda by multi-clinic, intergroup, double blind comparative
M, editor. Guidelines for treatment of nasal allergy - method. Ann Allergy. 1984; 53: 178-85.
Perennial Rhinitis and Pollinosis. Tokyo: Life Science 17. Baba K, Konno A, Takenaka H. Treatments. In: Okuda M,
Publishing; 2002. p. 8-11. editor. Guidelines for treatment of nasal allergy - Perennial
2. Shiozaki T, Sugiyama K, Nakazato K, Takeo T. [Effect of Rhinitis and Pollinosis. Tokyo: Life Science Publishing;
tea extracts, catechin and caffeine against type-I allergic 2002. p. 30-47.
reaction] [Article in Japanese]. Yakugaku Zasshi. 1997; 117: 18. Shoji T, Kanda T, Ikeda M, Akiyama H, Goda Y.
448-54. Bioavailability of apple procyanidins in rats. Polyphenols
3. Kotani M, Fujita A, Tanaka T. Clinical effect of persimmon Communications. 2004: 473.
leaf extract on Japanese cedar pollinosis. The Allergy in 19. Shoji T, Masumoto S, Moriichi N, Akiyama H, Kanda T,
Practice. 2000; 66: 398-402. Ohtake Y, Goda Y. Apple procyanidin oligomers absorption
4. Shigematsu N, Shen M, Hayamizu K, Kajimoto O, Takahashi in rats after oral administration: Analysis of procyanidins in
T, Shimosaka M, Okazaki M. A clinical study of the long- plasma using the porter method and HPLC/MS/MS. J Agric
term effect of foodstuff (gumi) containing tien-cha (Rubus Food Chem. 2006: 54: 884-92.
Suavissimus) and beef steak plant (Perilla Frutescens) for
Sugi-pollinosis. J Jpn Soc Clin Nutr. 2001; 23: 5-14.
5. Ukai K, Sakakura Y, Takeuchi K, Masuda S, Yuda A, Okawa
C, Ogata T. A clinical study of the effect of soft drink
containing tien-cha (Rubus Suavissimus) for Sugi-pollinosis.
Oto-rhino-laryngology (Tokyo). 1999; 42: 447-58.
6. Osada K, Ogino Y, Nakamura S, Kanda T, Yanagida T,
Sugano M. Effect of apple polyphenols on aggravation of
lipid metabolism induced by oxidized cholesterols. In:
Proceedings of the 39th Japanese Conference on the Yoko Nagasako-Akazome
Biochemistry of Lipids; 1997 Jun 13-14; Tokyo, Japan.
Tokyo: The Japanese Conference on the Biochemistry of Fundamental Research Laboratory
Lipids. 1997; 39: 317-20. Asahi Breweries Ltd
7. Osada K, Hoshina S, Nakamura S, Sugano M. Cholesterol 1-21, Midori 1-chome
oxidation in meat products and its regulation by Moriya-shi Ibaraki
supplementation of sodium nitrite and apple polyphenol 302-0106 Japan
before processing. J Agric Food Chem. 2000; 48: 3823-9. E-mail: yoko.akazome@asahibeer.co.jp

J Investig Allergol Clin Immunol 2006; Vol. 16(5): 283-289 © 2006 Esmon Publicidad