PharmacoNutrition Reviewed

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

Source: Am. J. Physiol. Heart Circ. Physiol. 04 JAN 2008 [Epub]
Article Type: Original Research

Authors: Angeloni et al.

The flavonoid quercetin (QU) is among the most common polyphenols found in the human diet. In the present study, Angeloni et al. assessed the in vitro effect of QU on the expression of more than 20.000 genes in cardiomyocytes.

The data, also this has not been directly discussed by the authors, suggest a hormetic effect of QU in this cell culture model, evident by the modulation of various phase II enzymes (such as HSP-32). These proteins, in turn, indirectly affect the cellular antioxidant defense system. i.e. render the cells better equipped for the occurrence of oxidative stress.

Although, in contrast to the authors, I think that the QU concentration tested (30 microM) is rather high (and certainly not in the physiological range), the article provides various interesting targets for the modulation of oxidative stress resistance of cardiomyocytes.

Let’s hope somebody dares to make the next step and assesses the impact of orally administered QU (and related flavonoids) and gene expression under in vivo conditions.

Image taken from: www.3dscience.com