Health effects of natural phenols and polyphenols
Because of the large structural diversity of dietary polyphenols, it is difficult to assert specific health effects from such ubiquitous substances. Their antioxidant activities in chemical and biological assays are undisputed, and many are associated with the health-promoting effects of fruits and vegetables, but to what extent these effects apply to entire organisms, and clinical outcomes in human disease in particular, remains a controversially discussed topic in nutrition science and disease prevention.
A review published in 2012 found growing consensus for the hypothesis that the specific intake of food and drink containing relatively high concentrations of flavonoids may play a meaningful role in reducing the risk of cardiovascular disease (CVD). The reviewers stated that research to date had been of poor quality and the large and rigorous trials are needed better to study the science, and to investigate possible adverse effects associated with excessive polyphenol intake: currently a lack of knowledge about safety suggests that polyphenol levels should not exceed that which occurs in a normal diet.
Toxicological concerns from dietary polyphenols have been voiced. They are unrelated to the acute toxicity of the phenols used in chemical industries. They are based on a number of in-vitro assays on the mutagenic and genotoxic properties of flavonols, such as quercetin. However, natural phenols and polyphenols are not classified as carcinogens. Their acute toxicity in humans and herbivores is generally very low due to their poor bioavailability. Tannins can have anti-feeding effects in livestock and interfere with nutrient absorption. This applies in particular to the astringent polyphenols and much less to the cinnamic and caffeic acid derivatives.
Questions on the relationship between health benefits and polyphenols generally revolve around bioavailability. Gallic acid and isoflavones are the most well-absorbed phenols, followed by catechins (flavan-3-ols), flavanones, and quercetin glucosides, but with different kinetics. The least well-absorbed phenols are the proanthocyanidins, galloylated tea catechins, and anthocyanins.
As interpreted by the Linus Pauling Institute and the European Food Safety Authority (EFSA), dietary flavonoids have little or no direct antioxidant food value following digestion. Unlike controlled test tube conditions, the fate of natural phenols in vivo shows they are poorly conserved (less than 5%), with most of what is absorbed existing as chemically-modified metabolites destined for rapid excretion.
||This section needs more medical references for verification or relies too heavily on primary sources. (October 2014)|
Many natural phenols, like the flavonoids, were found to be strong topoisomerase inhibitors in vitro, some of them were tested in vivo with similar results. Those substances share the properity with some chemotherapeutic anticancer drugs such etoposide and doxorubicin. When tested some natural phenols induced DNA mutations in MLL gene, which are common findings in neonatal acute leukemia. The DNA changes were highly increased by treatment with flavonoids in cultured blood stem cells. Maternal high flavonoid content diet is suspected to increase risk of particularly acute myeloid leukemia in neonates. Natural phenols have both anticarcinogenic - proapoptotic effect and a carcinogenic, DNA damaging, mutagenic potential. Adults seem to rapidly metabolize most of phenols, so toxic, mutagenic effects may not be pronounced in regular low doses intaken with food. Some natural phenols - EGCG, for example - were found to rapidly induce detoxyfying Nrf2 transcription factor activity, which seems to be responsible for observed beneficial, antioxidative effects of the substances and which also leads to rapid degradation of the phenolic molecules. However, the human embryo's detoxification system is not mature enough to deal with phenols, which can cross the placenta barier. High intake of flavonoid compounds during pregnancy is suspected to increase risk of neonatal leukemia. Therefore "bioflavonoid" supplements should be not used by pregnant women.
The Carcinogenic Potency Project, which is a part of the US EPA's Distributed Structure-Searchable Toxicity (DSSTox) Database Network, has been systemically testing the carcinogenicity of chemicals, both natural and synthetic, and building a publicly available database of the results since about 1980. At this time, none of the dietary phenols and polyphenols are classified as carcinogens. Some polyphenols, particularly from the flavan-3-ol (catechin-type), have both anticarcinogenic-proapoptotic and mutagenic effects. The DNA changes were increased by treatment with flavonoids in cultured blood stem cells. Some natural polyphenols share the properties of some anticancer drugs such as etoposide and doxorubicin while other polyphenols may induce DNA mutations in the MLL gene, which are common findings in neonatal acute leukemia.
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