Inhibitory effects of apple polyphenol extract (AP) and procyanidin contained in AP on in vitro pancreatic lipase activity and in vivo triglyceride absorption in mice and humans were examined. AP and procyanidin considerably inhibited in vitro pancreatic lipase activity. However, polyphenols, except for procyanidin, in AP (i.e., catechins, chalcones, and phenol carboxylic acids) showed weak inhibitory activities on pancreatic lipase. Procyanidins separated by normal-phase chromatography according to the degree of polymerization were also examined. Inhibitory effects of procyanidins increased according to the degree of polymerization from dimer to pentamer. On the other hand, pentamer or greater procyanidins showed maximal inhibitory effects on pancreatic lipase. These results suggested that with respect to in vitro pancreatic lipase inhibition, the degree of polymerization was an important factor and oligomeric procyanidin mainly contributed. Next, we performed a triglyceride tolerance test in mice and humans. Simultaneous ingestion of AP and triglyceride significantly inhibited an increase of plasma triglyceride levels in both models. These results suggested that the oligomeric procyanidins contained in AP inhibited triglyceride absorption by inhibiting pancreatic lipase activity in mice and humans.

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In the present study, a randomized, double-blind, placebo-controlled study was performed to evaluate the safety of an excessive intake and the effi cacy of a long-term intake of polyphenols derived from apples for moderately underweight to moderately obese subjects (long-term intake: 94 subjects; excessive intake: 30 subjects). For each trial, the subjects were divided into the following two groups: a group that drank beverages with apple polyphenols (600 mg) (hereinafter referred to as the apple group) and a group that drank beverages without apple polyphenols (hereinafter referred to as the placebo group). For the long-term intake trial, the subjects were given a regular amount of the beverage (340 g) each day for 12 weeks. For the excessive intake trial, the subjects were given three times the regular amount of the beverage each day for 4 weeks. It is noteworthy that the visceral fat area (VFA) of subjects in the apple group for the long-term intake trial had decreased signifi cantly by the 8-and 12-week marks (week 8: p < 0.05; week 12: p < 0.01) compared to the baseline (week 0). The degree of change in VFA experienced by subjects in the apple group compared to those in the placebo group was signifi cantly lower by the 8-and 12-week marks (p < 0.01). Stratifi ed analysis indicated that the VFA of subjects in the apple group that started with a high VFA (VFA > or = 100 cm 2 ) had decreased signifi cantly by the 8-and 12-week marks compared to the baseline (week 8: p < 0.05; week 12: p < 0.01). However, no signifi cant change in the VFA of subjects in the apple group that started with a normal VFA (VFA < 100 cm 2 ) was exhibited by the 8-and 12-week marks. No clinical problems arose in the blood examinations or physical examinations for the long-term intake trial or the excessive intake trial. No adverse reaction was observed in either trial. These results demonstrated the effi cacy and the safety of the beverage with apple polyphenols.

Apples contain many kinds of polyphenols, and the main components are oligomeric procyanidins. Applephenon is apple polyphenol extract produced commercially from unripe apples, and has been used as food additive in order to prevent oxidation of components in foods and its application in functional foods is expected. In a lipid metabolism regulation study, administration of Applephenon has the potential to exert strong anti-oxidative activity and to inhibit consumption of vitamin E and anti-oxidative enzymes. Double blind clinical trials of Applephenon on pediatric patients with atopic dermatitis, and tests using type I allergic model mice suggested that Applephenon might regulate allergic reactions. We found the no observed adverse effect level (NOAEL) of Applephenon is greater than 2000 mg/kg in a 90~day consecutive oral administration toxicity test in rats, and Applephenon is safe and acceptable based on mutagenicity tests.