Arginine + Glycine a Synergistic Duo for Gut Health

Lately, "gut health" has become a topic of interest way beyond colonics and irritable bowel syndrome. Scientists begin to understand more and more how important an intact intestinal system is for nutrient absorption, infection defense and general health. The results of a very recent study published in the Journal of Colerectal Disease (Picano. 2011) are thus relevant for all of us.

In an experiment with rats Picano et al. found that a combination therapy of l-arginine and glycine inhibited irradiation induced damage to the colon walls of the animals:

Stereologic analysis showed that irradiation induced a reduction of the total volume of the colon wall of group II and III animals compared to healthy controls, but not of group IV animals supplemented with glycine. The mucosal layer of the irradiated animals of all groups was reduced compared to healthy group I animals, but supplementation with L-arginine and glycine was effective in maintaining the epithelial surface of the mucosal layer.

Although I hope none of you is treated (or otherwise exposed) to similar doses of ionizing radiation, it certainly won't hurt your gut health to have an eye on your dietary intake of these two amino acids, in order to maintain optimal gut health.

L-Arginine Biscuits Exhibit Ameliorated Insulin Response. A Viable Alternative for People with Metabolic Syndrome!?

"L-Arginine ameliorates insulin resistance and has beneficial effects on blood pressure", "Fat people love cookies and tend to develop insulin resistance!" - if these two thoughts get together in the head of an Italian scientists, a new product is born: the L-Arginine Biscuit!

In a recent study Emanuela Setola (Setola. 2011) investigated the effect of a biscuit with 6.6g arginine on selected metabolic parameters of 7 healthy subjects. The results are encouraging:

A significant increase of nitric oxide (NOx) and cGMP levels were significantly increased with Biscuit +L-ARG 6.6 g and Powdered L-ARG as compared to Biscuit. AUC NOx and cGMP were significantly increased (p<0.04vs Biscuit). Percentage incremental increase of post-ischemic blood flow significantly increased with Biscuit +L-ARG 6.6 g and Powdered L-ARG, suggesting a functional effect of L-ARG added to the food preparation. Further, at 240 minute mean arterial blood pressure and peripheral vascular resistances slightly declined with Biscuit +L-ARG 6.6 g without reaching a statistical significance. At metabolic levels, the addition of L-ARG to a biscuit decreased insulin levels in the presence of similar glycemic levels, in particular a significant decrease of AUCinsulin during the test with Biscuit +L-ARG 6.6 g in comparison to Biscuit alone was found (p<0.05).

The last result, i.e. the decreased insulin release is probably the most interesting finding of this study and was further investigated by the researcher:

From the results of glucose and insulin, two indices were derived: a Modified Matsuda, (index of whole-body insulin sensitivity) and the Disposition Index (index of the product of insulin sensitivity and first phase insulin secretion). We were able to define that both indices were significantly increased with 6 Biscuits having 6.6 g of L-Arginine while intermediate values were found when 3 Biscuits (3.3 g) were eaten as compared to Biscuits without L-Arginine addition.

After all, I think it would be better to avoid cookies and biscuits completely, but if you just cannot resist, you may well add some arginine to the dough for this years Christmas baking.

3g BCAA + Arginine + Carbs Pre-Workout Modulates Hormonal Response to Single Bout of Treadmill Running to Exhaustion

BCAAs + Arginine + Carbohydrates before workout!? Sounds familiar, doesn't it? In fact many of the first generation preworkout products were either formulated like that or consumers were advised to stack them with a branched amino acid (BCAA) product of the same company. Studies which investigated the combined ergogenic effect of these nutrients are yet scarce. So, I thought that it would be worth posting the results of a recent study from China (Hsu. 2011).

Before they started exercising on a treadmill, the subjects, 14 male physical active college students, received a beverage containing either 3g of BCAA (2:1:1) + 0.5g Arginine + 12.1g carbohydrates or placebo. Blood samples of each subject were collected before exercise, 0, 10, 20, 40, 60, 120 min and 24 h after exercise and the procedure was repeated after two weeks (cross-over design). The results were as follows:

No significant differences in the levels of lactate, ammonia, creatine kinase and glycerol between the two groups were observed at any of the time points. However, the levels of glucose and insulin were significantly higher in the BA trial as compared to those in the PL trial at the 40 and 60 min recovery points. Furthermore, the testosterone to cortisol ratio at the 120 min recovery point was significantly higher in the BA trial as compared to that in the PL trial.

While higher glucose and insulin levels are hardly surprising in view of the fact that the placebo contained no calories whatsoever, the improved hormonal recovery (measured as testosterone / cortisol ratio) in the supplemented group appears to be pretty interesting.

A closer look at the exact data does yet reveal that the supplemented group had a higher testosterone / cortisol ratio to begin with. So, if we calculate the relative changes in the T/C ratio 120min after exercising to exhaustion, these are +13.2% in the placebo group and only +6.8% in the supplemented group.
Does that mean that the money you are spending on preworkout products is wasted? From a hormonal perspective, maybe. From a psychological perspective, we do yet still have another result of the study: "Fatigue score increased immediately at exhaustion in both groups, but the decrease in the fatigue score at 120 min recovery point was significant only in BA trial." Consequently, even if it does not improve the hormonal milieu in the early recovery period, supplementation with branched chain amino acids, arginine and carbohydrates could provide the psychological edge you need to drag yourself to the gym regularly ;-)

On a side note: It would have been interesting to see T/C levels measured beyond the 120 minutes post exhaustion. Based on the fact that the recovery of the T/C levels of the supplemented group sped up from T=60min to T=120min, one may well hypothesize that there would be measurable (hormonal) advantages for the BA group at T=180min and beyond.

AKG as in Arginine Alpha-Ketoglutarate for GI Health

For many of us, our gut is like our feet. We ignore it as long as it appears to be working properly. I think, I do not have to tell you that this is a mistake. Just like you cannot run without healthy feed, you cannot digest and use all the good food and supplements you consume without a healthy gut. This is why you should be interested in the findings of a recent review by scientists from the Hubei key Laboratory of Animal Nutrition and Feed Science in Wuhan 430023, China (Hou. 2011).


The scientists evaluation of related studies lead them to conclude that the conversion of Alpha-ketoglutarate (AKG), which is an intermediate of the Krebs cycle and bridges amino acid metabolism with glucose oxidation, into glutamate in the gastrointestinal tract of humans and animals is of particular interest in view of overall gastric functioning, "including regulation of cell function, neurotransmission, and gastric emptying".

Translating the basic research into practice, results of recent studies indicate that dietary supplementation with AKG alleviates oxidative stress and injury in intestinal mucosal cells, while improving intestinal mucosal integrity and absorption of nutrients in endotoxin-challenged pigs.

If you do not find that exciting, you might be interested in AKG's effect on mTOR-signaling (largely regarded as one of the fundamental triggers of protein synthesis and "muscle growth"):

The beneficial effects of AKG are associated with increased activation of the mTOR signaling pathway and net protein synthesis.

So, in view of the disappointing news on the inability of Arginine-AKG to raise nitric oxide levels, it may come as a surprise that it may have a distinct value far apart from muscle pumps and popping veins.

L-Citrulline Against Arterial Stiffness

You probably know it from the ingredient list of your pre-workout or amino acid product, l-citrulline. Being a possible precursor of l-arginine it is included in those formulas to increase nitric oxide levels and deliver those "skin bursting pumps" the advertisements brag about.

In a recent study, scientists from Japan (Ochiai. 2010) found that 1 week of l-citrulline supplementation at 5.6g/day effectively reduced arterial stiffness in 15 healthy males:

Compared with the placebo group, baPWV [index of arterial stiffness] was significantly reduced in the l-citrulline group (p<0.01). No significant differences in blood pressure (BP) were found between the two groups, and no correlation was observed between BP and baPWV. The serum nitrogen oxide (NOx, the sum of nitrite plus nitrate) and NO metabolic products were significantly increased only in the l-citrulline group (p<0.05). Plasma citrulline, arginine and the ratio of arginine/asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthase (arginine/ADMA ratio) were significantly increased in the l-citrulline group compared with the placebo group (p<0.05, p<0.01, p<0.05, respectively). Moreover, there was a correlation between the increase of plasma arginine and the reduction of baPWV (r=-0.553, p<0.05).

Beyond the reduction in arterial stiffness, these results confirm the hypothesis that l-citrulline effectively increases NO metabolism (probably even more than l-arginine) AND, what's even more important, reduces an endogenous inhibitor of NO synthase, so that more nitric oxide may be produced.