PharmacoNutrition Reviewed

Today I would like to introduce a new category which I wanted to add for quite some time already, i.e. book reviews. Not necessarily of brand new releases only, but also of those (older) publications that hopefully will provide you with same enlightenment and diversion I experienced while reading these books.

A couple of days ago I borrowed a rather small book (just about 200 pages) written by Adrian Woolfson and published in 2004, which carries the interesting title “An Intelligent Person’s Guide to Genetics”.

Let me cite from its preface:
“ (…) We are at the cusp of a new Enlightenment, defined by the accumulated genetic knowledge that enables us to entertain the possibility of modifying our own nature and of creating artificial life. The tremendous power for change is unprecedented. (…) My view is slightly different: the creation of synthetic life is an inevitability.”

Such a statement might invite to indulge in all too fantastic speculations about the future of (human) life on earth.
Instead, Woolfson takes you on a thrilling voyage though the origins, key principles and recent developments of genetics. For me, the book has been a real page-turner, especially due to the myriads of papers he cites (many of which I – sadly - haven’t heard about before) and anecdotes from the life of scientists whose groundbreaking work will change our life, maybe forever.

So, if you want to learn something about smart genes, the N-value paradox, how to make creatures from scratch, the Fibonacci pattern in plants, the hypothetical organism LUCA, the trade-off between olfaction and vision, why humans are natural-born dualists and how the one-by-one study of over one million fruit fly embryos can pave the way to the Nobel prize, than the books is just right for you.

In his last chapter ‘A Manifesto for Life’, Woolfson asks “Should we attempt to remodel ourselves?”

An absurd question.

Because “it is inevitable that someone somewhere will eventually create advanced synthetic life and modify human nature beyond all recognition. The intervening ethical and philosophical issues are important details – perhaps the most important that mankind will ever have to consider – but they are details nonetheless. (…) we are intrinsically curious, because we have utopian desires: these are inalienably human characteristics. (…) We may need to accept that humans and all other DNA-based life are not an end point in themselves, but contingent beginnings (…).“

Well said.

Source: J Neuroinflammation (2008), 5: 12 (open access)
Article Type: Original Research
Authors: X Chen et al.

A morning without coffee is unthinkable for me. And especially during the day in the lab I need the regular ‘perfusion’ with the black gold. A habit, which - based on the latest publication by Chen et al. - might not be that bad at all for me.

One of the earliest symptoms experienced by Alzheimer’s disease (AD) patients is olfactory dysfunction. The olfactory bulb is characterized by an intact blood brain barrier (BBB) that can get disrupted, e.g., when ingesting a high-cholesterol diet.
When testing such a diet (2% cholesterol) in rabbits, Chen et al. found that the daily administration of 3mg caffeine in the drinking water for 12 weeks “blocked high cholesterol diet-induced
* increases in extravasation of IgG and fibrinogen,
* increases in leakage of Evan’s blue dye
* decreases in levels of the tight junction proteins occludin and ZO-1
* increases in astrocytes activation and microglia density where IgG extravasation was present.”

“Our observations that caffeine had no effects on plasma levels of total cholesterol and HDL indicate that caffeine protects against high cholesterol diet-induced disruption of BBB downstream of cholesterol.”

“The protective effects of caffeine against high cholesterol diet-induced increases in BBB disruption might happen at the BBB per se, and the protective effects of caffeine against high cholesterol diet-induced increases in the density of astrocytes and microglia could be an indirect consequence of its protective effects against BBB disruption. On the other hand, it has been shown that caffeine (and adenosine) can regulate neuroinflammation in in vitro models devoid of BBB. Therefore, the protective effects of caffeine against high cholesterol diet induced increases in astrocyte activation and increases in density of microglia might parallel its protective effects against BBB disruption.”

From a practical point of view it is interesting to note that “the dose of caffeine (3 mg/day) used in this study for 3 to 4 kg rabbits is equivalent to an adult human weighing 70-80 kg consuming a single cup of coffee and is far less than the average caffeine consumption in the USA and Canada that is about 200 mg per person per day.”

The provisional PDF can be downloaded here.

Source: Journal of Gerontology (Biol. Sci.) 63A (2008): 242-252
Article Type: Original Research
Authors: I Lenaerts et al.

When working with C. elegans myself (limited times though) I didn’t break my head too much about the pros and cons of feeding them with heat-inactivated E. coli as long as each plate contained the same amount of food.
Well, I maybe should have given it another thought, at least based on the latest article by Isabel Lenaerts and colleagues.

Here, the authors “…describe convenient ways to exert DR (dietary restriction) by culture on agar plates containing axenic (i.e., there is no microbial food source) medium. We used these to explore whether effects of axenic culture really reflect DR. Our results imply that major nutrient components of axenic medium, and overall caloric content, are not limiting for life span. However, adding growth-arrested Escherichia coli as an additional food source rescued the effects of axenic culture. We then sought to identify the component of E. coli that is critical for normal C. elegans nutrition using add-back experiments. Our results suggest that C. elegans has a nutritional requirement for live, metabolically active microbes or, possibly, an unidentified, heat-labile, nonsoluble component present in live microbes.”

Of note also, the addition of Daucus carota and Pisum sativum extracts to axenic medium, e.g., increased fecundity without affecting lifespan. In contrast, increasing concentrations of autoclaved or sonicated E. coli had no effect on offspring number.
Also, radiation-arrested but metabolically active E. coli rescued the effect of axenic medium. This, however, was just seen for low-dose radiated E.coli, indicating that “…as long as some metabolically active E. coli remained, rescue was possible. This finding suggests the surprising conclusion that metabolic activity in its microbial food source is a nutritional requirement for C. elegans.”

Almost everything known regarding C. elegans can be found here: wormbook.org

In what they called a ‘critical appraisal’, 19 scientists from around the world (Canada, Finland, Portugal, Sweden, UK & USA) reevaluated the significance of carbohydrate restriction as a nutritional approach for controlling biochemical parameters in diabetes. The authors summarize that…

“…current nutritional approaches to metabolism syndrome and type 2 diabetes generally rely on reductions in dietary fat. The success of such approaches has been limited and therapy more generally relies on pharmacology. The argument is made that a reevaluation of the role of carbohydrate restriction, the historical and intuitive approach to the problem, may provide an alternative and possibly superior dietary strategy. The rationale is that carbohydrate restriction improves glycemic control and reduces insulin fluctuations which are primary targets. Experiments are summarized showing that carbohydrate-restricted diets are at least as effective for weight loss as low-fat diets and that substitution of fat for carbohydrate is generally beneficial for risk of cardiovascular disease. These beneficial effects of carbohydrate restriction do not require weight loss.
Finally, the point is re-iterated that carbohydrate restriction improves all of the features of metabolic syndrome.”

The review has been published OPEN ACCESS in Nutrition and Metabolism.

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

For those interested, here some brief information on a new book by Mark S. Meskin, Wayne R. Bidlack & R. Keith Randolph that’s going to be published in a few days (8 April 2008) by CRC Press.
That’s what you can expect from the book:

* Discusses the role of phytochemicals in healthy aging and disease prevention
* Covers polyphenols, flavonoid analysis, botanical therapeutics, chronic disease prevention, and more
* Presents the most current research for food companies and supplement manufacturers developing functional food
* Provides a section on personalized nutrition using nutrigenomics to determine nutrition therapy

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: BMC Medical Genomics (Open Access, 20 March 2008)
Article Type: Original Research
Authors: Pan Z et al.

Pterostilbene, a dimethylether analog of resveratrol, has long been known for its antioxidant, antifungal and antiinflammatory activities (to mention just a few). However, little is known on its mechanism(s) of action. In the present study, Pan et al. incubated S. cerevisiae (a common model organism for the identification of therapeutic compounds) with 70 µM (= IC50) pterostilbene prior running extensive transcript profiling experiments.
In a nutshell, pterostilbene affected the expression of >1000 genes (up: 1007; down: 182).

“We have identified the molecular pathways affected by pterostilbene, and our results show that pterostilbene affects the expression of a diverse group of genes in yeast cells.Using Gene Ontology-based analysis, the most significant effects were observed in genes involved in methionine metabolism, response to drug, transcription factor activity, and mitochondrion functions. Additional analyses indicated that many genes involved in lipid metabolism were also affected. The observed response of lipid metabolism genes is in agreement with the known hypolipidemic properties of pterostilbene mediated through the activation of PPARalpha. The induction of a large number of mitochondrial genes by pterostilbene is consistent with its previously-demonstrated role in apoptosis in human cancer cells.Our data also show that pterostilbene has a significant effect on methionine metabolism, perhaps resulting in the depletion of methionine by the inhibition of methionine biosynthesis. The effect of pterostilbene on methionine metabolism has not been previously observed and merits further investigation.”

The effects on methionine might be of particular interest, as methionine metabolism has also been linked to aging.
Does this possibly mean that resveratrol and its analogs enhance, e.g. C. elegans, lifespan by modulating methionine levels? PubMed, at least, does not provide a sufficient answer….

Today I would like to draw your attention to a website which (I think) deserves a lot of attention as it provides “a daily look behind the scenes of the work of Baby Milk Action on the boycott, other baby food companies and wider infant feeding issues.” The icon below shows the focus of the campaign.

Although the proper handling of infant formula might not be too much of a problem in industrialized countries, bottle feeding in so-called developing countries is indeed causing often more harm than good. 

“Formula for Disaster” is the title of a disturbing film released by UNICEF Philippines in 2007. I know, organizations like UNICEF also have to “earn” money and hence might exaggerate; but even if only a fraction is true it needs to be made public and denounced.

For more information please visit the respective blog.

Before going on holiday for the next two weeks, I would like to draw your attention to a recent review entitled “Nutritional Therapies for Mental Health Disorders” published by Lakhan and Vieira online in the Nutrition Journal (21 January 2008).

The authors conclude that “essential vitamins, minerals, and omega-3 fatty acids are often deficient in the general population in America and other developed countries; and are exceptionally deficient in patients suffering from mental disorders. Studies have shown that daily supplements of vital nutrients often effectively reduce patients’ symptoms. Supplements that contain amino acids also reduce symptoms, because they are converted to neurotransmitters that alleviate depression and other mental disorders. Based on emerging scientific evidence, this form of nutritional supplement treatment may be appropriate for controlling major depression, bipolar disorder, schizophrenia and anxiety disorders, eating disorders, attention deficit disorder/attention deficit hyperactivity disorder (ADD/ADHD), addiction, and autism.”

So far so good.

Although I am a nutritionist by training (and heart), I don’t like the following paragraph of the abstract: “Most antidepressants and other prescription drugs cause severe side effects, which usually discourage patients from taking their medications. Such noncompliant patients who have mental disorders are at a higher risk for committing suicide or being institutionalized. One way for psychiatrists to overcome this noncompliance is to educate themselves about alternative or complementary nutritional treatments.”

Having spent several years in a neuropharmacology lab, I got convinced that it is essential for the patients’ quality of life to take their drugs. Full stop. Admittedly, drugs have side effects; still, current neuropharmacological active compounds are very effective and in the majority of cases cannot be replaced by a dietary intervention. This, however, does not mean that diet might not be useful to

a) support an ongoing drug treatment (i.e. help to reduce the required dose or to ease side-effects) and

b) prevent the onset of some mental disorders in the first place.

So, rather than asking the question of “nutritional therapy vs. drug treatment”, a combined/complimentary approach of classical drugs and dietary intervention might be most effective for patients with mental health disorders. 

If you want to read more about mental health disorders, have a look here: Mental Health Blog

Image taken from: paho.org