Saturday, March 8, 2014

L-Arginine - 6g/Day Boost Cholesterol- & Non-Esterified Fatty Acid Lowering Effects of Resistance Training. Are Classic Pre-Workouts Actually "Health Supplements"?

Lifting will improve your blood lipids, l-arginine will boost the effect.
In the spirit of Tuesday's post on the potential negative effects of nitrate supplements on weight loss (learn more + see box below for some important clarifications), I would like to invite you to take a look at the effects of "short-term  L-arginine  supplementation  on  lipid  profile  and  inflammatory proteins after acute resistance exercise in overweight men" as they are about to be reported in one of the future issues of e-SPEN, the European e-Journal of Clinical Nutrition and Metabolism by Nascimento et al. (Nascimento. 2014) - it's not essentially new, but actually quite a nice reminder of the fat that what I said about l-arginine in the nitrate article was not all made up.
An addendum to the nitrate study: Even a persistent 5% reduction in RMR would not necessarily inhibit weight loss + you can argue that your body needs less energy / oxygen, because it works more effectively and contrary to common believe that's what a true ergogenic should do!
In the introduction to the said article, I already hinted at and linked to the potential weight loss benefits of l-arginine. In spite of the fact that it is literally useless as an NO-booster (remember without increase in NOS, the enzyme that produces NO from arginine, simply piling up more arginine in your blood will only lead to increases in uric acid), previous studies have already shown that L-arg improves the metabolic profile of people with suboptimal health status.
  • Schulze et al.. for example, observed that l-arginine speed up the triglyceride-lowering effect of simvastatin in patients with elevated plasma triglycerides (Schulze. 2009)
  • El-Kirsh et al. found that both, L‐arginine and L‐citrulline supplementation ameliorated the biochemical parameters and blunted arthesclerotic lesions in high‐fat and high‐cholesterol‐fed rats (El-Kirsh. 2011)
Other studies report beneficial effects on blood pressure and - as discussed in the anti-diabetes series - an ameliorating effect on the blood glucose levels of diabetic and/or insulin resistant individuals (McKnight. 2010; Dong. 2011).

So, the results of this most recent study don't really come as a surprise

In view of what we already knew about l-arginine, the results of the Nascimento study, i.e. reductions in  LDL cholesterol and NEFA levels, in response to the ingestion of 3x2g of pure l-arginine per day in this double blind, randomized crossover study don't come as a surprise.
Figure 1: Changes in triglycerides, total & LDL cholesterol and NEFA levels in response to exercise, only (control) and exercise + arginine (arginine) supplementation; figures in boxes ind. inter-group diff. (Nascrimento. 2014)
What's "news", though, is the interaction with exercise that sheds a whole new light the good old NO-Xplode (learn more, but keep in mind that one characteristic feature of this products is and was being totally underdosed) and its identical clones! I mean, who would have expected that he was buying a health supplement that potentiates the beneficial effects of exercise, in this case...
  • The official SuppVersity Supplement Shoot-Out!
    The longstanding veteran, NOXplode AVPT,
    is challenged by a clone of its own, 
    NOXplode 2.0 Advanced Strength -
    which will be the last pre-workout standing?
    four acute, machine-based resistance training sessions
  • stretching + general warm-up and cool down before / after sessions
  • three sets of 12 repetitions; 60% of the 1RM; 60s rest between sets
  • starting with large, ending with small muscle groups
  • large muscle groups: Chest press, leg press, pull down, leg extensions
  • small muscle groups: Deltoid machine, leg curl, biceps curl, triceps pulley
...on the potentially artherogenic low-density lipoprotein (LPL) and the amount of pro-diabetic non-esterified fatty acids in his bloodstream? You did? Well... I should have anticipated that, Mr & Mr Smar Alec ;-)
There is one question left to answer: What exactly is the mechanism here? I know that some of you won't care - as long as it works - but let's be honest, wouldn't it be nice to know? Well, acute and chronic exercise increase have already been shown to increase the activity of lecithin-cholesterol aciltransferase (L- CAT), the enzyme responsible for the cholesterol ester transfer to HDL, which will then evacuate the cholestrol from the circulation. If this effect is either increased or the transport facilitated by l-arginine, this would explain the reduction in LDL the researchers observed in the study at hand.

Figure 2: The short-term improvements in adiponectin Nascrimento et al. observed stand in line with the well-known long-term improvements in blood glucose management.
Moreover, studies by Tan et al. (2011) suggest that L-arginine will have direct effects on the expression of fat-metabolic genes in skeletal muscle and white adipose tissue, which favor lipogenesis in the muscle (not a problem if those lipids are subsequently burned as fuel during workouts) and a reduced storage of fat in the adipose organ. In conjunction with its proven ability to stimulate mitochondrial biogenesis and brown adipose tissue development (McKnight. 2010) and the previously discussed effects on WAT,  hyperphagia,  improved insulin sensitivity and - much contrary to nitrate (learn more) - increased energy expenditure (albeit only on low protein diets; Clemmensen. 2012). In sum these effects would appear to be profound enough to explain the observations in the study at hand, and those I reported in previous SuppVersity articles on l-arginine - specifically those discussing the potential fat burning (more) and anti-diabetic / glucose lowering effects (more).

Whether that's reason enough for you to begin supplementing again, is yet probably a question of your current metabolic state... if you are by no means like the seven overweight, hypertensive men, non-smoking and sedentary with a mean age of 46±5 yrs and a body weight of 93.1±12.0 kg, ain't insulin resistance, or have high cholesterol levels, it's pretty unlikely that you will see huge benefits.
  • Clemmensen, Christoffer, et al. "L-Arginine improves multiple physiological parameters in mice exposed to diet-induced metabolic disturbances." Amino acids 43.3 (2012): 1265-1275.
  • Dong, Jia-Yi, et al. "Effect of oral L-arginine supplementation on blood pressure: a meta-analysis of randomized, double-blind, placebo-controlled trials." American heart journal 162.6 (2011): 959-965.
  • El‐Kirsh, Amal Ashmawy Ahmed, et al. "The effect of L‐arginine or L‐citrulline supplementation on biochemical parameters and the vascular aortic wall in high‐fat and high‐cholesterol‐fed rats." Cell biochemistry and function 29.5 (2011): 414-428.
  • McKnight, Jason R., et al. "Beneficial effects of L-arginine on reducing obesity: potential mechanisms and important implications for human health." Amino acids 39.2 (2010): 349-357.
  • Schulze, Friedrich, et al. "L-Arginine enhances the triglyceride-lowering effect of simvastatin in patients with elevated plasma triglycerides." Nutrition research 29.5 (2009): 291-297.
  • Tan, Bie, et al. "Dietary L-arginine supplementation differentially regulates expression of lipid-metabolic genes in porcine adipose tissue and skeletal muscle." The Journal of nutritional biochemistry 22.5 (2011): 441-445.