PharmacoNutrition Reviewed

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: British Journal of Pharmacology 2007, Epub ahead of print
Article Type: Original Research
Authors: Schwedhelm et al.

Nitric oxide synthases (NOS) metabolize L-arginine (LA; semi-essential amino acid) to nitric oxide (NO) and L-citrulline (LC; non-essential amino acid). Due to its vasoactive activity, NO induces vasodilation of both arterial and venous blood vessels via activation of soluble guanylyl cyclase. Oral LA treatment in humans, however, is hampered by its extensive metabolism; furthermore LA’s efficiency is suggested to be influenced by its competition with the endogenous NOS inhibitor ADMA (asymmetric dimethylarginine), a phenomenon that has also been called the “arginine paradox”. Interestingly, LC, which does not undergo extensive presystemic and systemic elimination, can serve as an LA precursor. Following its uptake into the body, LA is converted to l-argininosuccinate by argininosuccinate synthase and subsequently to l-arginine by argininosuccinate lyase.
In their randomized, double-blind, placebo-controlled, cross-over study (n=20), Schwedhelm et al. assessed the pharmacokinetic and -dynamic properties of oral LC (and LA) intake. Major findings are:

* oral LC administration effectively increases plasma LA levels
* oral LC administration is well tolerated without side effects
* high dose LC treatment (3g) improves the LA:ADMA ratio
* only high dose LC treatment increases urinary nitrate and cGMP, thus indicating a modulation of NO metabolism

However, no significant effect of endothelial-dependant vasodilation (a secondary study goal) was found, possibly due to the good health status of the study subjects. The authors conclude that “our results provide a rationale for larger, prospective clinical studies with longer treatment periods to investigate the effects of oral l-citrulline supplementation on endothelial function in patients with endothelial dysfunction and vascular disease.”

Image taken from: student.ccbcmd.edu