Beyond Nitric Oxide II: Arginine & Citrulline Modulate Blood Lipids & Liver Fatty Acid Composition And Ameliorate Aortic Lipid Deposition in High Fat Fed Rats

Image 1: The mouse on the left probably
had too little arginine in its high fat diet
(just kiddin' ;-)
This is a follow up not on yesterday's third, but on the second installment of the Amino Acids for Super Humans series on Carl Lenore's Super Human Radio. In that episode I had already alluded to the metabolic benefits of arginine and citrulline supplementation, which reach far beyond their purported use as ergogenic aids and nitric oxide booster. A very recent study (El Kirsh. 2011) published a week ago ahead of print in the online issue of Cell Biochemistry & Function confirmed and expanded on the results of previous studies which showed beneficial effects on parameters of organ (specifically heart and liver) in rodent models.

6 groups of rats fed either a normal diet or the dubious "high fat" diet, scientists use to induce obesity along with the characteristic symptoms of the metabolic syndrome (insulin resistance, arteriosclerosis, etc.) were fed one of the following diets:
  • group 1: normal food, no supplement
  • group 2: normal food, arginine (100mg/kg; human equivalent 16mg/kg)
  • group 3: normal food, citrulline (100mg/kg)
  • group 4: high fat diet (HFD), no supplement
  • group 5: high fat diet (HFD), arginine (100mg/kg)
  • group 6: high fat diet (HFD), citrulline (100mg/kg)
Both the negative effects of the high fat diet, as well as the ameliorative effects of arginine and citrulline on serum transaminase levels (indicators of liver "activity" /high levels are mostly interpreted as signs of liver damage), triglycerides, cholesterol levels and indices of atherosclerosis were profound:
HFD feeding increased significantly serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities, urea and all lipid profiles and decreased significantly serum high-density lipoprotein-cholesterol (HDL-c) and non significantly serum nitric oxide levels. L-arginine or L-citrulline administration reversed the increase in serum AST and ALT activities, urea and all lipid profiles.

As it can be seen in figure 1, the positive effects of arginine and citrulline even went beyond the mere amelioration of the detrimental effects of the high fat diet by increasing HDL-c and nitric oxide levels, decreasing the count of dangerous V-LDL particles even compared to normal diet and modulating the relative percentages of 18 : 0, 20 : 0 and 22 : 6 to 16 : 0 fatty acids in the livers of the rats on the high fat diet.
Figure 1: Triglyceride and cholesterol levels of rats fed normal chow (control) and rats on a high fat diet (HFD) supplemented with either arginine (HFD+Arg) or citrulline (HFD+Cit) (data adapted from El Kirsh. 2011)

Moreover, the beneficial effects on heart health that are generally ascribed to such improvement in blood and tissue markers could actually be confirmed by light and transmission electron microscopic images of the thoracic aorta. While the HFD group that did not receive supplemental arginine or citrulline "demonstrated structural changes in the endothelial cells of the intimal layer, medial smooth muscle cells as well as in the adventitial layer", there was only "little structural alterations in animals supplemented with L-arginine or L-citrulline along with HFC feeding".

Taken together, these and the results I reported in the aforementioned episode of Amino Acids for Super Humans should well be able to change your perspective on your favorite pre-workout product forever - even if it does not give you the pump the fancy ad you saw when you bought it promised, it may well save your organs from the consequences of one or another dietary faux pas. I hope, I do not have to tell you, though, that it would border on or rather be plain nutritional idiocy, if you used arginine and citrulline to make up for the consumption of the famous westernized high fat, high carb, low protein fast food diet (which would be similar to the HFD the rats consumes)!
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