PharmacoNutrition Reviewed

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

Source: Am. J. Physiol. Regul. Integr. Comp. Physiol. (2007) [Epub]
Article Type: Original Research
Authors: Martin-Gronert et al.

This is now the third time I am writing about the impact of in utero and early postnatal nutrition on fitness in later life.  Whereas before we learned some new insights in how changes in maternal dietary iron or fat might affect offspring life, the new paper by Martin-Gronert et al. addresses the question how dietary postnatal protein levels regulate key molecules believed to markedly control the aging process.

When pups of normally-fed dams were nursed by low-protein-fed (8% vs. 20% in the control group; iso-caloric diets) dams, dramatic biochemical changes (measured at day 21 post partum) occurred that might explain the earlier reported increased lifespan in these animals. The authors not only found that insulin sensitivity was improved but also a significant upregulation (measured in kidney tissue) of IRbeta, IGF1-R, Akt1, Akt2 as well as SIRT1. In addition, the expression of important antioxidant enzymes, i.e. catalase, CuZnSOD and GPx1, was elevated.

Martin-Gronert et al. conclude that “the findings of this study are in agreement with Hormesis Hypothesis, which has been proposed to explain the life-extending action of calorie restriciton. The hypothesis postulates that a low-intensity biological stressor exerts defence responses in the organism that help protect it against the causes of aging. The enhanced coping with intense stressors and restriction of senescent deterioration lead to retardation of age associated diseases and increased longevity. It seems that a similar process may underlie the association between early nutrition and the aging process.”

A candidate for the effect of restricted protein intake on lifespan has also been recently identified by Naudi et al.: methionine (whose restriction leads to upregulation of uncoupling proteins (UCP4) and an increase in mitochondrial biogenesis).

Poor mums-to-be: your burden of doing things right during pregnacy and nursing are certainly on the rise.

Image taken from: jupiterimages.com

Source: JBC 7 Jan 2008 (Epub)
Article Type: Original Research
Authors: Cuddihy et al.

For many people vitamin E supplementation is still the magic bullet for preventing the onset of chronic diseases and even the maladies of aging. Although vitamin E in its various forms is certainly important for cell and organ function, the present paper by Cuddihy et al. is a nice example that mother nature created the activity pattern of biomolecules not in a one-way fashion but somewhat chaotic. But read yourself…..

“Vitamin E is the major lipid soluble chain-breaking antioxidant in mammals and plays an important role in normal development and physiology. Deficiency (whether dietary or genetic) results in primarily nervous system pathology, including cerebellar neurodegeneration and progressive ataxia (abnormal gait). However, despite the widely acknowledged antioxidant properties of vitamin E, only a few studies have directly correlated levels of reactive oxygen species with vitamin E availability in animal models. We explored the relationship between vitamin E and reactive oxygen species in two mouse models of vitamin E deficiency; dietary deficiency, and a genetic model (tocopherol transfer protein, Ttp-/-, mice).

Both groups of mice developed near-complete depletion of alpha-tocopherol (the major tocopherol in vitamin E) in most organs, but not brain, which was relatively resistant to loss of alpha-tocopherol. F4-neuroprostanes, an index of lipid peroxidation, were unexpectedly lower in brain of deficient mice compared to controls. In vivo oxidation of dihydroethidium by superoxide radical was also significantly lower in brain of deficient animals. Superoxide production by brain mitochondria isolated from vitamin E deficient and Ttp-/- mice, measured by electron paramagnetic resonance spectroscopy, demonstrated a biphasic dependence on exogenously added alpha-tocopherol. At low concentrations, alpha-tocopherol enhanced superoxide flux from mitochondria, a response which was reversed at higher concentrations.

Here we propose a mechanism, supported by molecular modeling, to explain decreased superoxide production during alpha-tocopherol deficiency, and speculate that this could be a beneficial response under conditions of alpha-tocopherol deficiency.”

Image taken from: dopaminejewelery.com

Source: J. Pediatr. (152) 2008: 79-84
Article Type: Original Research
Authors: Aaltonen et al.

Alcohol consumption and smoking have long been the only concerns regarding the time we spend in utero. This, however, changed with the publication of the so-called Barker hypothesis in the 1980s. Barker postulated that maternal under-/malnutrition might have long-lasting effects on the susceptibility and occurrence of various diseases (especially cardiovascular disease) in the life of their children (’fetal or in utero programming‘).

Aaltonen et al. studied the effect of fat-modified diets consumed during pregnancy on the blood  pressure of 6-month old infants (n=256). After dividing the dietary intake into quartiles and correcting for various confounding variables, the authors found:

1) a U-shape association maternal mono-unsaturated fatty acid (MUFA) intake and infant diastolic blood pressure

2) a U-shape association between maternal carbohydrate intake and infant diastolic and systolic blood pressure

“One of the most interesting findings in our study was the complex interaction between maternal carbohydrate intake and infant blood pressure. This finding may be linked to the pathogenesis of gestational diabetes in which altered glucose metabolism in the mother exposes the fetus to high levels of blood glucose and subsequent hyperinsulinemia. Due to the anabolic properties of insulin, hyperglycemia (even in temporary peaks) may lead to cardiac hypertrophy and functional abnormalities. Therefore, a high maternal carbohydrate intake, particularly consumption of refined carbohydrates in the diet, could result in subclinical maternal hyperglycemia and mild fetal hyperinsulinemia, resulting in higher blood pressure in infancy. This concept is supported by the observation that the higher systolic blood pressure in the neonatal period is linked to increased umbilical cord insulin concentrations, which may be driven by even minor maternal hyperglycemia. In view of the adverse fetal metabolic programming of intrauterine hyperglycemia in gestational diabetes in combination with a postnatal nutritional imbalance manifesting itself in a clustering of the cardiovascular risk factors at even early ages, the long-term sequelae of our finding warrant further investigation.”

Taken together, this study again indicates that the environmental conditions (i.e. maternal diet, body weight, etc.) we are exposed to in utero might be a lot more important for our teenage and adult life than many of us previously thought.

Image taken from: pregnancy.about.com