PharmacoNutrition Reviewed

Source: Chemistry & Physics of Lipids, 4 March 2008 [Epub]
Article Type: Review
Authors: Chapkin RS et al.

Cells, particularly those of the gastrointestinal tract, are exposed to a - often rapidly - changing environment. In their present review, Robert Chapkin and colleagues summarize how docosahexaenoic acid (DHA) and related fatty acids might help to maintain cell health in the colon:

“…we present data demonstrating that DHA selectively modulates the subcellular localization of lipidated signaling proteins depending on their transport pathway, which may be universally applied to other lipidated protein trafficking. An interesting possibility raised by the current observations is that lipidated proteins may exhibit different subcellular distribution profiles in various tissues, which contain a distinct membrane lipid composition. In addition, the current findings clearly indicate that subcellular localization of proteins with a certain trafficking pathway can be subjected to selective regulation by dietary manipulation. This form of regulated plasma membrane targeting of a select subset of upstream signaling proteins may provide cells with the flexibility to coordinate the arrangement of signaling translators on the cell surface. Ultimately, this may allow organ systems such as the colon to optimally decode, respond, and adapt to the vagaries of an ever-changing extracellular environment.”

Also noteworthy:

“Recently, the U.S. Food and DrugAdministration (FDA) has approved the use of a health claim on labels for foods containing DHA. As part of an ongoing commitment to provide consumers with innovative-healthy products, food companies are now scrambling to incorporate omega-3 fatty acids into a range of novel commercial foods in order to provide for the wider public consumption of DHA. It is both appropriate and timely, therefore, to precisely determine how DHA modulates cell signaling networks and reduces the risk of developing colon cancer and intestinal inflammatory disorders.”

Source: Breast Cancer Research (2007), 9: 201
Article Type: Review
Authors: M Gago-Dominguez, X Jiang, JE Castelao

Image taken from: http://www.massgeneral.org/cancer/crr/types/breast/
illustrations/images/breast_lymph.jpg

In most experimental settings and disease states, lipid peroxidation, notably HNE, MDA or isoprostanes, are considered to be detrimental for the survival of the affected cells/tissue/organ.
The review by Gago-Domingeuz et al., however, summarizes compelling evidence that, at least in the case of breast cancer, in might just be the other way around.
Whereas enhanced lipid peroxidation promotes the onset of liver, kidney and skin cancer as well as of neurodegenerative diseases, the same process seems to protect women from falling ill with breast cancer. Even more surprising is the fact that quite a number of food constituents well known to reduce harmful oxidative and nitrosative stress appear to promote lipid peroxidation in breast cancer cells. Let’s look, for example, at marine omega-3 fatty acids and green tea. The authors refer to a previous publication “of results in humans implicating the peroxidation products of marine omega-3 fatty acids as the proximal anticarcinogens.” In terms of tea, Gago-Dominguez and colleagues conclude “that the protective effect of tea on breast cancer was confined to those possessing the low-activity genotype of the antioxidant catechol-O-methyl transferase (COMT), putatively because more beneficial peroxidation agents could reach the cancer cell and cause damage”.
Admittedly, this is a hypothesis, but one really worth thinking about, especially as the presented evidence is quite strong. What I am missing, though, is a bit more elaboration on how the dietary constituents exert their antidromic biological activities, which are nonetheless always in favour of an individual’s health.
Is it maybe still just a matter of our genes?

Source: Nutrition & Metabolism (2007), 4: 5 (Open Access)
Article Type: Original Research
Authors: W Zhou, P Murkerjee, MA Kiebish, WT Markis, JG Mantis, TN Seyfried

Image taken from:
http://3quarksdaily.blogs.com/3quarksdaily/images/brain_21.jpg

Ketogenic diets have been in clinical use for more than 80 years, primarily for the symptomatic treatment of epilepsy. In contrast to other organs, the brain almost exclusively needs glucose to satisfy its energy requirements. As an alternative, the brain can utilize ketone bodies for generating energy and fuelling its metabolism. Normal, healthy brain cells can better cope with this shift in energy source than tumour cells. Admittedly, to combat malignant brain cancer this way is a smart idea, especially as it appears so simple by using principles of evolutionary biology. And the concept works well, at least in this preclinical study on mice with implanted brain tumours. Mice fed a ketogenic diet displayed reduced glucose and enhanced ketone levels, finally causing the starvation of cancer cells. Cancer cells are also quite susceptible to oxidative stress; ketones, however, reduce the production of reactive oxygen species (ROS), as shown in neurons exposed to glutamate excitotoxicity (Maalouf et al.).
Of note, the same, i.e. the shift from glucose to ketone body metabolism, also happens in times of caloric restriction which has been shown to enhance the life span of many animal species.
All in all, the issue of using ketone bodies and ketonic diets for improving human health is quite promising, although much still needs to be done to fully understand the nature of their biological action.

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.