PharmacoNutrition Reviewed

Source: British Journal of Pharmacology 2007, Epub ahead of print
Article Type: Original Research
Authors: Schwedhelm et al.

Nitric oxide synthases (NOS) metabolize L-arginine (LA; semi-essential amino acid) to nitric oxide (NO) and L-citrulline (LC; non-essential amino acid). Due to its vasoactive activity, NO induces vasodilation of both arterial and venous blood vessels via activation of soluble guanylyl cyclase. Oral LA treatment in humans, however, is hampered by its extensive metabolism; furthermore LA’s efficiency is suggested to be influenced by its competition with the endogenous NOS inhibitor ADMA (asymmetric dimethylarginine), a phenomenon that has also been called the “arginine paradox”. Interestingly, LC, which does not undergo extensive presystemic and systemic elimination, can serve as an LA precursor. Following its uptake into the body, LA is converted to l-argininosuccinate by argininosuccinate synthase and subsequently to l-arginine by argininosuccinate lyase.
In their randomized, double-blind, placebo-controlled, cross-over study (n=20), Schwedhelm et al. assessed the pharmacokinetic and -dynamic properties of oral LC (and LA) intake. Major findings are:

* oral LC administration effectively increases plasma LA levels
* oral LC administration is well tolerated without side effects
* high dose LC treatment (3g) improves the LA:ADMA ratio
* only high dose LC treatment increases urinary nitrate and cGMP, thus indicating a modulation of NO metabolism

However, no significant effect of endothelial-dependant vasodilation (a secondary study goal) was found, possibly due to the good health status of the study subjects. The authors conclude that “our results provide a rationale for larger, prospective clinical studies with longer treatment periods to investigate the effects of oral l-citrulline supplementation on endothelial function in patients with endothelial dysfunction and vascular disease.”

Image taken from: student.ccbcmd.edu

Source: Science 317: 516-519
Article Type: Original Research
Authors: Outeiro et al.
As members of the histone deacetylase family of proteins, sirtuins play a prominent role in aging. Seven sirtuins, SIRT1 to SIRT7, have been identified in humans.
Most research on sirtuin-mediated modulation of life span focussed on the activation of sirtuins (especially SIRT1), e.g. via resveratrol, a stilbene present in red wine and other food plants.
In the July 27 issue of Science, Outeiro et al. now report on the rescue of alpha-synuclein-induced neurotoxicity in models (cell cuture and Drosophila m.) of Parkinson’s disease (PD) due to inactivation of SIRT2. The mechanism of action might be due to 1) alterations in alpha-synuclein aggregation and 2) microtubule stabilization. Whether SIRT2 inactivation also directly affects life span, however, has not been addressed in this article. Those interested in this aspect might want to have a look at a recent paper published by Wang et al. (Aging Cell 6(4), 2007), where the authors descibe elevated SIRT2 expression in response to caloric restriction, a classical ‘inducer’ of longevity.

If you are looking for more information on PD, have a look at the PD Blog Network.

Image taken from: www.pdmdcenter.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