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: Aging Cell (2007), 6: 15-25
Article Type: Original Contribution
Authors: TG Valencak, T Ruf

Image taken from:
http://www.macvillage.de/blog/wp-content/uploads/2006/07/dali_zeit.jpg

Omega-3 fatty acids (n-3) are generally considered as health-beneficial (see also post discussed yesterday). When talking about the lifespan of mammals, however, n-3 fatty acids seem to hamper longevity. The reason for this correlation has been linked to:
• the high susceptibility of polyunsaturated fatty acids (PUFA; n-3, n-6) to oxidation
• the boost in basal metabolic rate (BMC) in the presence of PUFA, e.g. by up-regulating the activity of membrane-associated proteins
These effects have been summarized in the ‘membrane pacemaker theory of aging’: PUFA (up) –> BMR (up) –> longevity (down).

After correcting for body weight and phylogenetic effects, Valencak & Ruf found a clear correlation between the ratio of n3:n6 in muscle and maximum lifespan (MLS), based on the analysis of 42 mammalian species. Noteworthy, MLS was unrelated to docosahexaenoic (DHA, n-3) content, total membrane unsaturation as well as BMR, thus questioning the ‘membrane pacemaker theory of aging’.
Does this mean now that we should avoid consuming PUFAs, particularly n-3?
I would say no, because the current recommendation (see also Simopoulos, 2006) to increase dietary n-3 intake is largely based on the discrepancy in the composition of ingested dietary fat between western societies (n-3:n-6 = 1:15) and our hunting & gathering ancestors (n-3:n-6 = 1:1). Hence, the risk of reducing your (maximum) lifespan by consuming n-3-rich plant and animal foods (which consequently will enhance your n-3:n-6 ratio) is rather small.

Source: Critical Care Medicine (2007), 35: 544-554
Article Type: Original Contribution
Authors: MB Schaefer, J Ott, A Mohr, MH B, A Grosz, N Weissmann, S Ishii, F Grimminger, W Seeger K Mayer

Image taken from: http://doreen.mkbmemorial.com/NF/photos/ICU.JPG

Most intensive care patients are sooner or later affected by the systemic inflammatory response syndrome (SIRS). Hallmark of SIRS is the elevated production of certain eicosanoids possessing strong pro-inflammatory properties. Eicosanoids are derived from its precursor arachidonic acid, an omega-6 (n-6) fatty acid commonly found in biological membranes.
Arachidonic acid (20:4, n-6) in turn can be synthesizes from linoleic acid (18:2, n-6), the main fatty acid found in soy oil-based lipid emulsions, such as Lipoven (Fresenius Kabi, Germany). In contrast, cold water fish are rich in omega-3 fatty acids (especially eicosapentaenoic and docosahexaenoic acid), which are generally considered to show anti-inflammatory activity.
In their recent article, Schaefer et al. compare in a model of murine acute lung injury the inflammatory effect of Lipoven with that of the n-3-rich lipid formulation Omegaven (Fresenius Kabi, Germany). In agreement with previous reports, Lipoven promotes the production of pro-inflammatory biomarkers whereas the application of Omegaven leads to opposite effects. Here it is important to note that the impact of both formulations depends on the experimental design, i.e. the permanent infusion of the mice with the lipid emulsions. The authors point out that it is questionable whether the same effects could be provoked by oral intake of either lipid formulation.
Mechanistically, the article provides an interesting insight in the regulation of inflammation. Platelet-activating factor (PAF)-receptor knock-out mice (-/-) showed an inflammatory response comparable to those of wild type mice. However, neither Lipoven nor Omegaven were able to module the production of inflammatory biomarkers in PAF -/-, suggesting that both PAF and PAF-receptor are important for communicating the molecular signals exerted by n-3- and n-6.
In a nutshell, the administration of lipid emulsions might not only be means to supply the critically ill with enough energy, but also help to modulate the immune system towards pro- or anti-inflammatory response.

Another interesting report on the effect of n-3 in ICU patients can be found on the webpage of the Children’s Hospital Boston.