**1. Introduction**

Polyphenols are molecules with multiple hydroxyl groups that have been shown to provide numerous health benefits including reduction of inflammation, metabolic control and anti-cancer properties. Polyphenols can be found in a variety of natural sources such as cinnamon, green tea, coffee, vegetables and fruits. Although some evidence exists for the mechanisms of polyphenol molecules that lead to these health benefits, there is still much unknown about how these compounds act to alter metabolism, inflammation levels and cancer pathways. Some research suggests epigenetic modifications that alter expression level of disease state genes explain the benefits, while others identify potential signaling pathway and transcription factor targets affected by polyphenols or their metabolites as the method of control. One difficulty in researching the potential for polyphenol based therapies is the tremendous crossover between pathways that can affect multiple metabolic actions

ranging from dysregulation of metabolism to loss of cell cycle control. On top of the multi-targeted effects from signaling, epigenetic modifications can be detected and identified but not always possible to predict. Although the field of dietary therapeutics provides a much needed alternative to many other treatments, the uncertainty of use in certain cultures make it a challenging research topic but all the more important to tackle.

Some of the most commonly studied polyphenols include the catechin group. Available evidence suggests that some forms have higher activity on some targets but the active forms differ from target to target. For example, it has been suggested that resveratrol, which is a fused ring complex between two catechin molecules, binds to and modulates the allosteric effects of Sirt1 thus playing a role in deacetylation/acetylation of multiple targets [1–3]. The metabolic regulator FoxO1 is a transcription factor that is deacetylated by Sirt1 thus changing metabolic function as well as cell death pathways [4]. Modified catechins known as epigallocatechin gallate (EGCG) are found in high levels in green tea and have been shown to modify the epigenome of MCF7 breast cancer cells [5]. Observed results show multiple types of epigenetic modifications including both methylation of the DNA and acetylation of histones. Compounds found in cinnamon include polyphenol A, a linked dual catechin, which has been studied as a potential insulin mimic compound [5]. Additional compounds found in cinnamon include rutin, an acid labile bond between quercetin and epicatechin that have been predicted to interact with Sirt1 [1]. Additionally cinnamon has been shown to increase expression of both GLUT4 expression and translocation in adipose and muscle, although the responsible component of cinnamon has not been identified with certainty [6, 7].

The collection of evidence suggesting that natural products provide profound therapeutic benefits is growing. Although pharmaceutical industries have developed drugs that are effective at treating symptoms of metabolic dysregulation and inflammation, the majority of these medicines are focused on symptom management and targeted effects. The spectrum of benefits that are possible with polyphenol based therapies offer a potential to treat multiple disease states by targeting the root cause of disease. There is still much to be learned about how the effects of polyphenols can be predicted and if cross reactivity exists that could benefit one disease state but hurt another. However, the likelihood of reciprocal effects of a therapeutic is less likely when one known effect is beneficial on a broad scale than if the polyphenol therapy were aimed at controlling only one target. As many people become concerned about potential side effects of pharmaceuticals, some find comfort in alternative medicine such as polyphenols.
