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Safety and Toxicity  
Apple polyphenol extracts are listed ("apple essence, natural") in the FDA's approved additive/GRAS (Generally Recognized As Safe) database. They are presently used in concentrated levels in health supplements in Japan.


  • Japanese researchers found that apple polyphenol extracts are safe, even at concentrations 200 times the recommended human dosage.

  • Researchers at Cornell University recommend adding apple polyphenol powder to foods to promote good health.

Characteristics and physiological functions of polyphenols from apples, Biofactors. 2004;22(1-4):311-4.
The toxicology and safety of apple polyphenol extract, Food Chem Toxicol. 2004
Apple peels as a value-added food ingredient, J Agric Food Chem. 2003
Toxicological studies on procyanidin B-2 for external application as a hair growing agent, Food Chem Toxicol. 1999


Biofactors. 2004;22(1-4):311-4.
Characteristics and physiological functions of polyphenols from apples.

Akazome Y.

Fundamental Research Laboratory, Asahi Breweries, Ltd., 1-21, Midori 1-chome, Moriya-shi, Ibaraki 302-0106, Japan.

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.

PMID: 15630302 [PubMed - in process]
Food Chem Toxicol. 2004 Jun;42(6):959-67.

The toxicology and safety of apple polyphenol extract.

Shoji T, Akazome Y, Kanda T, Ikeda M.

Fundamental Research Laboratory, Asahi Breweries, Ltd., 1-21, Midori 1-chome, Moriya-shi, Ibaraki 302-0106, Japan.

Apple polyphenol extract has strong antioxidant activity and various physiological functions, and is used in Japan as a food additive and nutritional supplements. Here, we tested the consumption safety of Applephenon, which is a polyphenol extract produced from unripe apples. The Ames test without S9 mixture revealed that Applephenon, had slight mutagenicity at a high concentration of 2500 microg/plate; however, both chromosomal aberration test and the micronucleus test found no significant mutagenicity. Furthermore, an acute oral-toxicity test, and a 90-day subchronic-toxicity test showed no significant hematological, clinical, chemical, histopathological, or urinary effects at a dose of 2000 mg/kg. These results confirm that Applephenon is safe and no toxic at average dietary level.

PMID: 15110105 [PubMed - indexed for MEDLINE]


J Agric Food Chem. 2003 Mar 12;51(6):1676-83
Apple peels as a value-added food ingredient.
Wolfe KL, Liu RH.

Institute of Comparative and Environmental Toxicology, Cornell University, Ithaca, New York 14853-7201, USA.

There is some evidence that chronic diseases, such as cancer and cardiovascular disease, may occur as a result of oxidative stress. Apple peels have high concentrations of phenolic compounds and may assist in the prevention of chronic diseases. Millions of pounds of waste apple peels are generated in the production of applesauce and canned apples in New York State each year. We proposed that a valuable food ingredient could be made using the peels of these apples if they could be dried and ground to a powder without large losses of phytochemicals. Rome Beauty apple peels were treated with citric acid dips, ascorbic acid dips, and blanches before being oven-dried at 60 degrees C. Only blanching treatments greatly preserved the phenolic compounds, and peels blanched for 10 s had the highest total phenolic content. Rome Beauty apple peels were then blanched for 10 s and dried under various conditions (oven-dried at 40, 60, or 80 degrees C, air-dried, or freeze-dried). The air-dried and freeze-dried apple peels had the highest total phenolic, flavonoid, and anthocyanin contents. On a fresh weight basis, the total phenolic and flavonoid contents of these samples were similar to those of the fresh apple peels. Freeze-dried peels had a lower water activity than air-dried peels on a fresh weight basis. The optimal processing conditions for the ingredient were blanching for 10s and freeze-drying. The process was scaled up, and the apple peel powder ingredient was characterized. The total phenolic content was 3342 +/- 12 mg gallic acid equivalents/100 g dried peels, the flavonoid content was 2299 +/- 52 mg catechin equivalents/100 g dried peels, and the anthocyanin content was 169.7 +/- 1.6 mg cyanidin 3-glucoside equivalents/100 g dried peels. These phytochemical contents were a significantly higher than those of the fresh apple peels if calculated on a fresh weight basis (p < 0.05). The apple peel powder had a total antioxidant activity of 1251 +/- 56 micromol vitamin C equivalents/g, similar to fresh Rome Beauty peels on a fresh weight basis (p > 0.05). One gram of powder had an antioxidant activity equivalent to 220 mg of vitamin C. The freeze-dried apple peels also had a strong antiproliferative effect on HepG(2) liver cancer cells with a median effective dose (EC(50)) of 1.88 +/- 0.01 mg/mL. This was lower than the EC(50) exhibited by the fresh apple peels (p < 0.05). Apple peel powder may be used in a various food products to add phytochemicals and promote good health.

(more research)

Food Chem Toxicol. 1999 May;37(5):545-52.
Toxicological studies on procyanidin B-2 for external application as a hair growing agent.

Takahashi T, Yokoo Y, Inoue T, Ishii A.

Tsukuba Research Laboratories, Kyowa Hakko Kogyo Co., Ibaraki, Japan.

Procyanidin B-2 [epicatechin-(4beta --> 8)-epicatechin] is one of condensed tannin that exists widely in plants. We have reported previously that procyanidin B-2 possesses hair epithelial cell growth-promoting activity and stimulates anagen induction in hair cycle progression. To evaluate the safety of topical procyanidin B-2 as a hair growing agent, we examined the mutagenicity, acute subcutaneous injection, primary irritation, skin sensitization, and eye irritation of this compound. Mutagenicity tests using bacteria showed procyanidin B-2 to be non-mutagenic. Chromosomal aberration tests using CHL cells indicated that procyanidin B-2 caused polyploidy but no structural aberrations. In micronucleus tests for mutagenicity using mice, procyanidin B-2 was negative. Acute subcutaneous injection study using rats revealed no symptoms of significant injury. The lethal dose of procyanidin B-2 is greater than 2000 mg/kg (subcutaneous injection). Primary irritation tests using rabbits indicated that procyanidin B-2 containing preparation shows no primary irritation. In the guinea pig maximization test, there was no evidence of sensitization to procyanidin B-2. In primary ocular irritation tests using rabbits, procyanidin B-2 containing preparation and vehicle showed slight irritation of conjunctivae which is assumed to be caused by ethanol. It is suggested that topical procyanidin B-2 is safe and acceptable from the series of toxicological tests.

PMID: 10456683 [PubMed - indexed for MEDLINE]
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