PharmacoNutrition Reviewed

In her article “Polyphenols have Great Potential but Not Enough Science“, Shane Starling comments on the recent advances and non-advances experienced during the 4th International Conference on Polyphenols Applications held in Malta:

“1. Clinicals: While there are hundreds of products the world over touting their polyphenol content, it was clear the science is not there for most of them, and that includes foods, beverages, cosmetics, supplements and pharmaceuticals. And these guys should know, being scientists and all. ………..” Read more at FFN

Source: Am. J. Physiol. Heart Circ. Physiol. 04 JAN 2008 [Epub]
Article Type: Original Research

Authors: Angeloni et al.

The flavonoid quercetin (QU) is among the most common polyphenols found in the human diet. In the present study, Angeloni et al. assessed the in vitro effect of QU on the expression of more than 20.000 genes in cardiomyocytes.

The data, also this has not been directly discussed by the authors, suggest a hormetic effect of QU in this cell culture model, evident by the modulation of various phase II enzymes (such as HSP-32). These proteins, in turn, indirectly affect the cellular antioxidant defense system. i.e. render the cells better equipped for the occurrence of oxidative stress.

Although, in contrast to the authors, I think that the QU concentration tested (30 microM) is rather high (and certainly not in the physiological range), the article provides various interesting targets for the modulation of oxidative stress resistance of cardiomyocytes.

Let’s hope somebody dares to make the next step and assesses the impact of orally administered QU (and related flavonoids) and gene expression under in vivo conditions.

Image taken from: www.3dscience.com

Another conference on the advances of polyphenol research, though smaller in size than the one in Japan, will take place in Malta, 14-16 November 2007.

Here a summary of the conference features:
“After the great success of the Polyphenols 2006 conference, the International Society for Antioxidants in Nutrition and Health (ISANH) organizes the 4th international meeting to gather high level scientists and professionals to give an update of advances in polyphenols benefits and promising trends of their use in improvement of human health. The conference offers an excellent opportunity to exchange ideas and experiences between researchers and industrialists. (…)
* Latest advances in polyphenols benefits in human health
* Latest advances in the role of polyphenols in chronic diseases prevention and therapy with focus on promising role on diabetes, obesity and aging management
* New solutions to optimize polyphenols processing and to better evaluate and improve their bioeffeciency in finished products
* New sources, ingredients and technlogical solutions in polyphenols industrial application (food, beverage, cosmetic and pharmaceutical industries)
We look forward to welcome you in Malta for this particular event.” Pr Joseph Bannister and Dr Marvin Edeas

Image taken from: www.isanh.com

For all those of you who are still thinking of submitting an abstract to the 3rd INTERNATIONAL CONFERENCE ON POLYPHENOLS AND HEALTH (ICPH 2007) taking place at the ICC Kyoto (Japan) from November 25-28, 2007, please be reminded that the deadline for abstract submission is June 30 !!!!

“(…) In recent years, much attention is internationally being denoted to polyphenols and health. Augustin Scalbert initiated International Conference on Polyphenols and Health in Vichy, France four years ago. It really stimulated and encouraged many people engaging in polyphenols on human health. The 2nd Conference at Davis, United States, was also a true success, and I would like to take this opportunity to thank Andrew Waterhouse and Cesar Fraga who organized this really fruitful conference. Nowadays, polyphenols are recognized as essential functional food factors and prevailed from the dining tables to medicinal uses. However, more scientific evidence should be required for understanding the optimal levels of their intake and the safety as well as the functionality. We believe 3rd Conference is necessary to discuss these subjects among the participants who are key contributors to the fields. (…)” Junji Terao, President of Organizing Committee.

Image taken from: ICPH 2007

Source: Trends in Neuroscience (2006), 29: 632-639
Article Type: Review
Authors: MP Mattson, A Cheng

Image taken from: http://www.bad-bad.de/gesch/paracel.gif

Recently, the hormesis theory is gaining momentum for explaining the health-beneficial effects of diets rich in fruits and vegetables. Actually, one of the first to describe hormetic effects of any substance applied to living things has been Paracelsus, one of the most famous scientists of the 16th century.
What is hormesis? The term describes the induction of health-beneficial effects due to the low-dose presence of agents that are toxic at higher concentrations (adaptive response). In this regard, phytochemicals (such as polpyhenols) can be considered as mild stressors provoking the up-regulation of the endogenous antioxidant network. This in turn would enable an organism to better cope with an increasing production of reactive oxidative and nitrosative species (ROS and RNS), for example in disease states. Consequently, the detrimental degeneration of proteins, fatty acids, sugars and DNA would be avoided. In the long run, this could finally lead to a healthier aging process, characterised by a lower burden of chronic, lifestyle maladies. Mattson and Cheng support this concept by summarising recent data obtained with, amongst others, the neurohormetic phytochemicals resveratrol and curcumin in vitro and in vivo.

Personally, I feel quite comfortable with this theory. However, whether it will help to answer the recurring question of whether an increase/decrease in biomarkers such as antioxidant capacity or antioxidant enzyme activity upon incubation/intake of phytochemicals is actually beneficial or detrimental, only time will tell.

For further reading, I recommend: Arumugam et al., 2006 and Hipkiss, 2006 and Hayes, 2007.

Source: Current Pharmaceutical Biotechnology (2006), 7: 483-494
Article Type: Review
Authors: R. Lupu, J.A. Menendez

Image taken from: http://herbal-nutrition.net/images/vegetables.jpg

Food plant-derived inhibitors of fatty acid synthase (FAS), such as EGCG (a polyphenol) from green tea, have been suggested as a new family of anti-cancer agents. In contrast to normal cells, tumor cells (especially those forming epithelial cancers) exhibit FAS hyperactivity to meet their increased demand of energy and membrane building blocks. Inhibition of FAS leads to tumor cell growth arrest and ultimately cell death (partly via apoptosis).
When talking about the inhibition of tumor cell growth and proliferation due to incubation with polyphenols (and related substances) one, however, has to keep in mind two potential pitfalls:
a) Polyphenols at medium to high concentration have been shown to cause artificially augmented release of cytotoxic reactive oxygen species (ROS) by reacting with various constituents of routinely used serum-supplemented culture media (Chai et al.).
b) The bioavailability of polyphenols is limited so that oral polyphenol intake gives plasma concentrations of approx. 0.5-5 µM. Many (actually too many) in vitro studies test polyphenol working solutions with concentrations far beyond the aforementioned physiological levels (Kroon et al.).
This are just two reasons for the failure of polyphenols to show their potentially health-beneficial effects in most intervention studies.
Now, Lupu & Menendez summarize recent data on the in vitro anti-tumor efficiency of polyphenols, i.e. quercetin, luteolin, kaempferol and EGCG, linked to the inhibition of FAS. At a concentration of 5 µM, these polpyhenols block FAS activity by >60% (Brusselmans et al.). Lupu & Menendez also provide an interesting overview on both molecular mechanisms (i.e. end-product starvation, accumulation of a toxic FAS substrate, altered membrane synthesis) as well as on molecular markers (i.e. p53, erbB-2 oncogene expression, PI-3′K/AKT pathway regulation) of FAS inhibition.
Thus, the pharmaconutritional regulation of FAS activity might represent a new alley for the diagnosis, prevention and possibly therapy of certain cancers.