PharmacoNutrition Reviewed

The latest issue of PNAS contains a collection of more than a dozen articles on reactive oxygen species (ROS):

“(…) The contents of this Special Feature on Reactive Oxygen Species in Chemistry and Biology represents a sampling of the excellent work that is being carried out at this important interface of chemistry and biology by using a wide range of chemical, kinetic, spectroscopic, and biological approaches. The authors come from several different fields and use a wide diversity of techniques and experimental systems; nevertheless, their studies all relate to the fundamental chemical reactivity of dioxygen and species derived from it.”
  

For the last couple of days I have been digging myself through I don’t know how many webpages and articles in search of the truth: to fear cholesterol or not to fear.

What a mess!
And what a shame to be part of the biomedical research field.
Whenever I thought that I had a somewhat clear picture it got rapdily destroyed by opening the next webpage or article PDF.
It seems that the whole field of pharmaco-nutritional medicine has gone crazy.
And that’s a terrible pity because nutrition - at least that’s what almost everone agrees on - can help to maintain your health. If we only would know how!

Coming back to the topic of this blog entry: if you are interested to obtain some critical information on the importance of cholesterol for human health and the impact & efficiency of cholesterol-lowering interventions (e.g. statins), I recommend you have a look at the THINCS webpage.

“For decades, enormous human and financial resources have been wasted on the cholesterol campaign, more promising research areas have been neglected, producers and manufacturers of animal food all over the world have suffered economically, and millions of healthy people have been frightened and badgered into eating a tedious and flavorless diet or into taking potentially dangerous drugs for the rest of their lives. As the scientific evidence in support of the cholesterol campaign is non-existent, we consider it important to stop it as soon as possible.
The International Network of Cholesterol Skeptics (THINCS) is a steadily growing group of scientists, physicians, other academicians and science writers from various countries. Members of this group represent different views about the causation of atherosclerosis and cardiovascular disease, some of them are in conflict with others, but this is a normal part of science. What we all oppose is that animal fat and high cholesterol play a role. The aim with this website is to inform our colleagues and the public that this idea is not supported by scientific evidence; in fact, for many years a huge number of scientific studies have directly contradicted it.”

If you are now interested in a critical analysis of Thincs’ critical view, read Robert Todd Carroll’s comment here.

Last but not least, a very interesting re-assessment of the current evidence regarding the cholesterol/heart link can be found at Science-Based Medicine.org (including more than 300 comments on this subject).

And I still insist, the whole discussion of whether cholesterol is good or bad for your heart and brain and I don’t know what else caused a terrible mess, especially for those who are confronted with a diagnosis that requires some kind of action.

It seems that there’s still a long way to go before we can move on from believing to knowing what cholesterol actually does or does not to our human body.

Source: Neuroscience Letters 439 (2008): 208-211
Article Type: Original Research
Authors: Kushida S et al.

In their latest paper, Kushida and colleagues examined in Amyloid beta-infused rats the effect of soft-diet feeding on two parameters which are typically affected in Alzheimer’s Disease (AD) patients

a) the release of the neurotransmitter dopamine
b) the learning ability and memory performance

Rats were fed either a hard (standard) or soft diet for 3 weeks days. During the last 2 weeks, rat brains were continuously infused with Abeta, the putative main culprit in AD.

“We found no significant differences in the basal level of dopamine release in the hippocampus between soft- and hard-diet-fed groups; however, the dopamine release evoked by high-K Ringer’s solution was significantly different between the soft- and hard-diet-fed groups. The increase of dopamine release in the hard-diet-fed group reached 420%; however, that in the soft-diet-fed group reached only 260%. In AD model rats, dopamine release in the soft-diet-fed group was significantly less than that of the hard-diet-fed group.”

After assessing the rats in the co-called step-through passive avoidance test, the authors conclude that:

“Our results also suggest that soft-diet feeding impairs learning ability and memory in AD rats; however, the underlying mechanism is unknown. One possible explanation is that the present results may be caused by the changes of activity in sensori-motor pathways of soft-diet-fed rats.”

How does this now relate to AD patients?

“Elderly people lose many teeth as they age. The loss of teeth not only forces them to eat soft foods, but also correlates to the development of senile dementia and Alzheimer’s disease (AD).”

So might one speculate that a rather early move in life towards the consumption of soft food triggers the onset of AD? An interesting idea – although much research is needed to establish this link of cause and consequence.

More on AD and diet (i.e. coffee intake) can be found here.

I don’t know whether many of you already read this article. As it is not (yet?) listed in the PubMed and has been published in a rather new journal (Current Aging Science) most probably not.
Anyway, I very much liked reading the review by Alberto Sanz and Rhoda Stefanatos (University of Tampere, Finland) which again deals with the pros and cons of the Mitochondrial Free Radical Theory of Aging (MFRTA).

“The Mitochondrial Free Radical Theory of Aging (MFRTA) proposes that mitochondrial free radicals, produced as by-products during normal metabolism, cause oxidative damage. According to MFRTA, the accumulation of this oxidative damage is the main driving force in the aging process. Although widely accepted, this theory remains unproven, because the evidence supporting it is largely correlative. For example, long-lived animals produce fewer free radicals and have lower oxidative damage levels in their tissues. However, this does not prove that free radical generation determines life span. In fact, the longest-living rodent -Heterocephalus glaber- produces high levels of free radicals and has significant oxidative damage levels in proteins, lipids and DNA.

In summary, available data concerning the role of free radicals in longevity control are contradictory, and do not prove MFRTA. In fact, the only way to test this theory is by specifically decreasing mitochondrial free radical production without altering other physiological parameters (e.g. insulin signalling). If MFRTA is true animals producing fewer mtROS must have the ability to live much longer than their experimental controls.”

The full text article is available here.