Wednesday, September 24, 2014

L-Ornithine an Anti-Stress Agent: Lower Cortisol, Higher DHEA, Better Sleep W/ Only 400mg of Ornithine Pre-Bed. Plus: Mini-Review of Add. Benefits - Burns, Gut Health, etc.

Stressed? Maybe ornithine can help. Or is this study just a hoax!?
Sounds like marketing shenanigan, right? "Lower Cortisol, Higher DHEA, Better Sleep W/ Only 400mg of Ornithine Pre-Bed." Ok, if it was marketing it would probably say "with only 5g of ornithine." I mean, 400mg that's not enough to generate significant revenues - is it?

But before we get to the marketing side of things, let's first look at the science, researchers from the Research Laboratories for Health Science & Food Technologies present in a recent paper in the Nutrition Journal, an open-access journal which charges scientists a certain fee for processing their papers.
You can learn more about sleep and the circadian rhythm at the SuppVersity

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In their 8 week study, Mika Miyake et al. provided fifty-two apparently healthy Japanese adults who had previously felt slightly stressed and fatigue with either L-ornithine (400 mg/day) or placebo capsules.

The participants were advised to take one (400mg) capsule everyday before going to bed for eight weeks. At the end of the study period, all participants arrived at the laboratory fasted for blood sampling and a handful of other tests.
Figure 1: Effect of L-ornithine supplementation on serum stress markers.Means of the change from 0 weeks of each stress marker level (A, DHEA-S; B, cortisol; C, cortisol/DHEA-S) to 2, 4, and 8 weeks: mean ± SE. White circles (○) indicate the placebo and black circles (●) indicate L-ornithine. (Miyake. 2014)
The blood was analyzed for serum cortisol and DHEAS levels. In addition, the perceived mood and quality of sleep were measured by the Profile of Mood States (POMS) tests, the Athens Insomnia Scale (AIS), and Ogri-Shirakawa-Azumi sleep inventory MA version (OSA-MA).
Figure 2: Effect of L-ornithine supplementation on OSA.Means of the change from 0 weeks of each OSA score (A, sleepiness on rising; B, initiation and maintenance of sleep; C, frequent dreaming; D, refreshing; E, sleep length) to 1, 2, 3, 4, 5, 6, 7 and 8 weeks: mean ± SE. White circles (○) indicate the placebo and black circles (●) indicate L-ornithine
Significant changes were observed for serum cortisol levels and the cortisol/DHEA-S ratio. Both were significantly decreased in the L-ornithine group in comparison with the placebo group. The POMS and OSA-MA tests (not shown in Figure 1) revealed that similar beneficial effects occurred for anger (sign. reduced) and perceived sleep quality, which were both improved in the L-ornithine group compared to the placebo group.
Is there anything else ornithine is good for? Sugino et al. report that l-ornithine supplementation (2-6g/day) attenuates physical fatigue in healthy volunteers by modulating lipid and amino acid metabolism (2008). It enhances wound healing in mice and man (Shi. 2002; Coudray-Lucas. 2000). It improves muscle protein synthesis after surgery (Wernerman. 1987). Just like arginine, it holds the potential to improve gut health (Cynober. 1994; de Oca. 1997; Raul. 1995). But it is, unlike arginine, is no insulin secretagogue (=won't trigger an insulin release; Bucci. 1992) - Bottom line: Lots of potential, but nothing that would make it a "must have" supplement.
Quite impressive results, considering the fact that we are talking about a minimal amount of an amino acids fitness enthusiasts know mainly as an ineffective growth hormone booster (Lambert. 1993). What did you say? "Bias"? Well, the product used in the study is produced by the Kyowa Hakko Bio Company a company that is an affiliate of Kirin Company Limited, to which the authors belong, but that does not mean that the results are inaccurate.

Nevertheless, I would advise you to keep it in mind before you buy a 5kg bag of ornithine as an anti-stress treatment for the next 10 years - maybe 25g for an 8-week test-run are a better idea. Not necessarily because of a potential bisa, but rather in view of the small number of study participants  and the fact that we don't know exactly the mechanism that triggers the increase in DHEA, decrease in cortisol and overall anti-stress effect.
Even in animal models, where similar effects on the HPTA have been observed (Kurata. 2012), it is not clear, whether all this may in fact be a result of the  influence L-ornithine has on the urea cycle (converts ammonia to urea in the liver), as some scientists apparently believe. Overall, we are thus dealing with an interesting finding, but one that needs independent confirmation from a larger trials, and one I would have significantly more faith in if I know exactly how it came about (mechanistically) | Comment on Facebook!
References:
  • Bucci, L. R., et al. "Ornithine supplementation and insulin release in bodybuilders." International journal of sport nutrition 2.3 (1992): 287-291. 
  • Coudray-Lucas, Colette, et al. "Ornithine [alpha]-ketoglutarate improves wound healing in severe burn patients: A prospective randomized double-blind trial versus isonitrogenous controls." Critical care medicine 28.6 (2000): 1772-1776.
  • Cynober, L. "Can arginine and ornithine support gut functions?." Gut 35.1 Suppl (1994): S42-S45.
  • de Oca, Javier, et al. "Effect Of Oral Supplementation Of Ornithine-[Alpha]-Ketoglutarate On The Intestinal Barrier After Orthotopic Small Bowel Transplantation." Transplantation 63.5 (1997): 636-639.
  • Kurata, Koji, et al. "Orally administered l-ornithine reduces restraint stress-induced activation of the hypothalamic-pituitary-adrenal axis in mice." Neuroscience letters 506.2 (2012): 287-291.
  • Lambert, M. I., et al. "Failure of commercial oral amino acid supplements to increase serum growth hormone concentrations in male body-builders." International Journal of Sport Nutrition 3.3 (1993): 298-305.
  • Miyake, Mika, et al. "Randomised controlled trial of the effects of L-ornithine on stress markers and sleep quality in healthy workers." Nutrition Journal 13.1 (2014): 53.
  • Raul, Francis, et al. "Functional and metabolic changes in intestinal mucosa of rats after enteral administration of ornithine α-ketoglutarate salt." Journal of Parenteral and Enteral Nutrition 19.2 (1995): 145-150.
  • Shi, Han Ping, et al. "Effect of supplemental ornithine on wound healing." Journal of Surgical Research 106.2 (2002): 299-302.
  • Sugino, Tomohiro, et al. "L-ornithine supplementation attenuates physical fatigue in healthy volunteers by modulating lipid and amino acid metabolism." Nutrition research 28.11 (2008): 738-743.
  • Wernerman, J., et al. "Ornithine-alpha-ketoglutarate improves skeletal muscle protein synthesis as assessed by ribosome analysis and nitrogen use after surgery." Annals of surgery 206.5 (1987): 674.