Ornithine supplement benefit and side effects
November 20 2016 by
Ray Sahelian, M.D.


L ornithine is an amino Acid used by the body to make arginine, proline, and polyamines. Ornithine is not an amino acid coded for by DNA, and is not involved in protein synthesis. Ornithine, therefore, is not found in protein.


Ornithine can be made as a byproduct when the enzyme arginase metabolizes arginine to  urea. Hence, ornithine is a prominent part of the urea cycle, which allows for the disposal of excess nitrogen. Most commonly, nitrogen is ingested through foods that contain protein.

The Urea Cycle
The main use of the urea cycle is to make arginine, so as an intermediate in metabolic processes, ornithine is quite important. Ornithine, via the action of ornithine decarboxylase, is the starting point for the synthesis of polyamines such as putrescine.

     Ornithine decarboxylase (ODC) is a key enzyme in polyamine biosynthesis. Increased polyamine levels are required for growth, differentiation, and transformation of cells.

Arginine versus ornithine
Is one amino acid preferbable to the other? Ornithine supplementation may be helpful in cases of burn injury and wound healing. At present, I don't have enough of an understanding to know under which circumstances it would be appropriate to supplement with it. Since ornithine can be made from arginine, supplementation with arginine may be sufficient or a good replacement. You may also consider ornithine alpha ketoglutarate supplements.


Ornithine alpha-ketoglutarate (OKG) information
Ornithine alpha-ketoglutarate is a salt formed of 2 molecules of ornithine and 1 alpha-ketoglutarate. Its administration improves nutritional status in chronically malnourished (e.g., elderly) and acutely malnourished patients (especially burn and trauma patients). There is evidence that OKG activity is not the simple addition of the effects of ornithine and alpha-ketoglutarate (alphaKG), because the presence of both moieties is required to induce the generation of key metabolites such as glutamine, proline, and arginine, whereas this does not occur when one or the other is given separately. For years, ornithine alpha-ketoglutarate activity has been associated with its ability to induce the secretion of anabolic hormones, such as insulin and growth hormone, and to increase glutamine and polyamine synthesis. Recent studies using chemical inhibitors of nitric oxide synthase (NOS) suggest that nitric oxide derived from arginine could be partly involved in OKG activity.

     Theoretically, alpha-ketoglutarate is a precursor of glutamine, a fact that may be of importance given the key regulatory properties of this amino acid. Although the literature suggests that glutamine synthesis accounts only for a marginal part of the disposal of exogenously supplied alpha-ketoglutarate, administered alpha-ketoglutarate has a potent 'sparing' effect on endogenous glutamine pools. When alpha-ketoglutarate is supplied as an ornithine salt, a synergistic effect of the two parts of the molecule increases the synthesis of glutamine or the 'sparing' of endogenous glutamine pools. In addition, alpha-ketoglutarate in combination with ornithine dramatically increases the synthesis of arginine, proline and polyamines, which also play key roles in metabolic adaptation to trauma. The administration of alpha-ketoglutarate in combination with ornithine improves gut morphology and functions, counteracts trauma-induced dysimmunity and exerts anabolic/anticatabolic actions on protein metabolism.


Coadministration of Ornithine and alpha-Ketoglutarate Is No More Effective Than Ornithine Alone As an Arginine Precursor in Piglets Enterally Fed an Arginine-Deficient Diet.
J Nutr. 2007. Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, Canada.
Simultaneous administration of alpha-ketoglutarate and ornithine, in a 1:2 molar ratio, may improve the effectiveness of ornithine as an arginine precursor in neonatal piglets by shifting ornithine metabolism away from oxidation and toward the synthesis of arginine and other metabolically important compounds. To study this proposed mechanism, enterally fed piglets were allocated to receive 1 of 4 diets for 5 d: an arginine -deficient diet (basal), or the basal diet supplemented with either alpha-ketoglutarate, ornithine, or both ornithine and alpha-ketoglutarate. The diets did not affect plasma arginine or ammonia concentrations, arginine flux, or arginine synthesis from ornithine. Therefore, arginine synthesis was not increased by the simultaneous infusion of ornithine and alpha-ketoglutarate. Piglets that received dietary ornithine had a 2-fold greater rate of proline synthesis from ornithine and oxidized a greater portion of the infused ornithine than piglets in the basal and +alpha-KG groups. Overall, ornithine addition to an arginine deficient diet had a greater effect on ornithine and arginine metabolism than the addition of alpha-ketoglutarate. First-pass intestinal metabolism was critical for ornithine synthesis and conversion to other metabolites but not for ornithine oxidation.


Ornithine, Arginine, and Human Growth Hormone release

Certain amino acids, such as arginine and ornithine, can stimulate the release of growth hormone when infused intravenously or administered orally. Some individuals ingest amino acids before strength training workouts, thinking that this enhances exercise-induced growth hormone release, thereby promoting greater gains in muscle mass and strength. There is a wide range of response of growth hormone release to amino acid administration between different people. A number of factors are involved including training status, sex, age, medications, other supplements, and diet. Although IV administration consistently leads to increased circulating growth hormone concentration, oral doses that are great enough to induce significant growth hormone release are likely to cause stomach discomfort and diarrhea. Ornithine may have to be ingested in massive amounts, such as 30 grams orally, to have any effect on growth hormone release, and even then, the release may be temporary.
     During exercise, intensity is a major determinant of growth hormone release. Up to now, studies have not consistently found that pre-exercise oral amino acid supplementation enhances growth hormone release. In addition,, no major studies have found that oral supplementation with arginine or ornithine before strength training increases muscle mass and strength to a greater extent than strength training alone. The use of specific amino acids to stimulate growth hormone release by athletes is probably not worthwhile.


Sleep effect
Nutr Res. 2013. Ornithine ingestion improved sleep disturbances but was not associated with correction of blood tryptophan ratio in Japanese Antarctica expedition members during summer. Department of Environmental Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan. Members of expeditions to Antarctica may show changes in biological and physiological parameters involved in lipid, glucose, and thyroid hormone metabolism as they adapt to the environment; however, alterations in amino acid (AA) levels and sleep among expedition members in Antarctica have yet to be fully elucidated. We hypothesized that there would be alterations of blood AA levels, and ornithine ingestion would affect biological parameters and sleep in Japanese expedition members during the summer in Antarctica. Japanese Antarctica Research Expedition members (22 people) who stayed in Antarctica for 3 months were examined, and a randomized double-blind study of Orn ingestion (400 mg/d) for 4 weeks was performed. Sleep conditions were evaluated subjectively by the Oguri-Shirakawa-Azumi (brief version) questionnaire. The blood of Japanese Antarctica Research Expedition members in Antarctica showed higher creatine kinase, lactate dehydrogenase, and ammonia levels than that in Japan. On blood AA analysis, aspartate, Orn, and serine were significantly higher, and alanine and tryptophan (Trp) were significantly lower in Antarctica than in Japan. The Trp ratio, the value of Trp divided by the sum of phenylalanine, tyrosine, and branched-chain AAs, was significantly lower in Antarctica than in Japan. Although sleep deteriorated during the stay in Antarctica, Orn ingestion, to some extent, improved sleep compared with the placebo group in Antarctica, suggesting that Orn is effective for people with heavy physical workloads in places such as Antarctica.



Aging Clin Exp Res. 2013. The new metabolic treatments for sarcopenia. In terms of managing sarcopenia, many studies have shown that physical activity (in particular resistance exercise) and specific nutrition interventions such as protein and amino acids supplementation can improve muscle mass and strength in older adults. Moreover, several drugs have been suggested to have an impact on muscle outcomes, with various levels of scientific evidence. In the present paper we have reviewed the evidence regarding the effect of some new metabolic agents (vitamin D, leucine, β-hydroxy β-methylbutyrate, citrulline malate, ornithine, isoflavones) on sarcopenia and muscular outcomes in older adults. For each metabolic agent, we have also discussed the biological plausibility of the described effect.


Prev Nutr Food Sci. 2015. The Effect of L-Ornithine on the Phosphorylation of mTORC1 Downstream Targets in Rat Liver.


Clinical efficacy of L-ornithine-L-aspartate in the management of hepatic encephalopathy.
Metab Brain Dis. 2002.
The clinical efficacy of both oral and parenteral L-ornithine-L-aspartate (OA) was confirmed by randomized, placebo-controlled, double-blind studies in patients with manifest hepatic encephalopathy and hyperammonemia. The drug was able to reduce high blood ammonia levels induced either by ammonium chloride or protein ingestion or existing as a clinical complication of cirrhosis per se. Furthermore, OA improved performance in Number Connection Test-A as well as mental state gradation. In contrast to the positive effects observed in patients with more advanced hepatic encephalopathy, oral OA does not seem to affect minimal hepatic encephalopathy. In a recent trial, OA decreased protein breakdown and stimulated protein synthesis in muscle. The therapy had little side effects, increasing with higher intravenously administered dosages, and was well tolerated after oral and parenteral administration.


Cancer therapy and prevention by green tea: role of ornithine decarboxylase.
Amino Acids. 2002.
Epidemiological studies revealed that the incidences of stomach and prostate cancers are the lowest in the world among a population that consumes green tea on a regular basis. It has also been reported that the quantity of green tea consumed, plays an important role in reducing cancer risk and in delaying cancer outbreak and recurrence. Various systems were used to confirm anti-cancer activities of green tea and/or EGCG. These included experimental animals in which cancer was induced chemically. Cultured cells transformed chemically or by oncogenes were also used. These studies clearly demonstrated that green tea or EGCG have anticancer and cancer preventive properties. The mechanisms of these activities have also been studied in details. It has been shown that green tea and its active components interfere with signal transduction pathways. Thus the activities of various protein kinases are inhibited, the expression of nuclear proto-oncogenes declines and the activity of ornithine decarboxylase (ODC) is reduced. ODC, which catalyzes the rate-limiting step in the biosynthesis of polyamines is closely linked with cellular proliferation and carcinogenesis. Inhibitors of ODC, like alpha-difluoromethylornithine (DFMO) have long been used for cancer prevention and therapy. It has been suggested that polyamine depletion by green tea could offer one explanation for its anti-cancer activities.


Macrophage arginine metabolism to ornithine/urea or nitric oxide/citrulline: a life or death issue.
Crit Rev Immunol. 2001.
Department of Surgery and Diabetes Institute for Immunology and Transplantation, University of Minnesota Hospitals and Clinics, Minneapolis
Macrophages can metabolize arginine to nitric oxide in quantities that inhibit pathogens or nearby host cells. They can instead metabolize arginine to ornithine (a precursor of polyamines and collagen) in quantities that stimulate pathogens or nearby host cells. Macrophages are essentially the only circulating cells that can make these life or death decisions with arginine. Macrophages expressing these destructive or constructive phenotypes have been termed M-1 or M-2 because they also stimulate TH1 or TH2 responses, respectively. Factors that influence whether a macrophage expresses the M-1 or M-2 phenotype and the real or potential impact on immune responses and other host processes are discussed.


Can arginine and ornithine support gut functions?
Gut 1994.
Arginine and ornithine are precursors of nitric oxide and polyamines, respectively. These metabolites intimately participate in permeability and adaptive responses of the gut. The liver possesses high arginase activity as an intrinsic part of urea synthesis and would consume most of the portal supply of dietary arginine. The gut reduces this possibility by converting dietary arginine to citrulline, which effectively bypass the liver and is resynthesized to arginine in the kidney. Dietary ornithine supplementation, in the form of ornithine alpha-ketoglutarate (OKG) can be considered as an arginine precursor. Several supplement studies have shown both amino acids to promote growth hormone and insulin secretion with anabolic effects in postoperative patients. Their intermediary metabolites (for example, glutamine, proline) may also be of benefit in trauma metabolism. Specific effects of either amino acid on the gut are poorly reported. One recent animal study showed improved morphology after OKG administration, perhaps through increased polyamine secretion. Generation of nitric oxide from arginine has two facets. Excess production from high dose arginine potentiated the effects of experimentally induced sepsis, whereas low doses improved survival. These considerations suggest that the role of enteral diet supplementation with arginine or OKG should be urgently examined for any benefits it may have on mucosal barrier function.

5-htp can cause intestinal discomfort

Source Naturals buy L-Ornithine Powder, 3.53 oz (100 g)

Free-Form Powder Amino Acid Supplement

L-Ornithine, a free-form crystalline amino acid, is a precursor of arginine, which is necessary for the synthesis of creatine, an important energy provider for muscles. In addition, it is a key compound in the urea cycle, one of the body's main processes for eliminating ammonia.

Suggested Use: 1/2 teaspoon L Ornithine powder daily between meals, or as recommended by your health care professional.
Supplement Facts:
Serving Size: 1/2 Teaspoon (approx. 1.9 g)
Servings Per Container: 52
Amount Per Serving
Calories 10
L-Ornithine HCl 1.9 g


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