Ornithine Alpha-Ketoglutarate (OKG) Promotes Glutamine and Muscle Mass

Ornithine alpha-ketoglutarate (OKG) has many benefits including maintaining muscle mass by encouraging the production of glutamine!

Are you a little worried about losing muscle mass?

Is your strength beginning to wax and wane?

If yes, you are like millions of other aging baby boomers and OKG may be just what you are looking for!

Ornithine alpha-ketoglutarate (OKG) is a supplement that has been around for awhile. It is being studied for its many virtues including maintaining muscle mass , but that was not always the case. (ads)

Back in the 1960s, researchers were concerned about coma patients who had a buildup of ammonia levels. They believed that if alpha ketoglutarate interacted with the ammonia, it would form glutamate and ultimately lower these levels. They were wrong, but they discovered something fascinating. OKG improved the patients nutritional status. They reported that the nitrogen balance and plasma amino acid profile improved. 1

Wow! This was great news not only for coma patients that needed to preserve muscle mass but for others who faced muscle loss or other clinical- related conditions. Researchers got busy and studied the role of OKG on preserving muscle and protein. They examined its influence on the hormones, insulin and growth factor, which are involved in muscle growth. And they began to understand the value of OKG in increasing muscle mass.

What is OKG?

OKG is an ionic salt made up of one molecule ornithine and two molecules of alpha-ketoglutarate. OKG has been reported to speed up healing time among burn patients and those with severe wounds, such as post-operative patients. Other studies have examined its role in cancer, gut health, chronic malnourishment among the elderly, childrens’ growth in disease states and those with a compromised immune system. It has also been examined among healthy individuals who want to maintain or increase muscle mass.

How does OKG work?

Researchers are still scratching their heads trying to figure out how OKG works. They have observed that the two components of OKG are precursors to glutamate, which can be converted to glutamine. Glutamine plays a role in regulating protein metabolism. Ornithine is used by the body to make arginine, proline and the polyamines such as putrescine, spermine and spermidine. These play a role in successfully helping cells reproduce and helping to repair wounds. Ornithine is also a component of the urea cycle. Researchers also think that OKG decreases protein breakdown and the markers of protein degradation such as in burn injuries. They suspect that it might stimulate the release of insulin and growth hormone. And lastly; researchers report that the effects seen with OKG are seen when both ornithine and alpha-ketoglutarate are present together but not when they are used separately. 2

OKG has been studied in both human and animal models and has been shown to be beneficial in several conditions including trauma and compromised health conditions.

Burn Patients

In burn patients, muscle proteins are broken down and plasma ammonia and amino acids increase in the urine. As a result, weight decreases and patients experience muscle wasting. This breakdown produces a negative nitrogen balance. As healing occurs, these compounds return to normal.

However, when OKG is given to burn patients in the amount of 10g–30g, several studies have shown that the process of wound healing increases. 3 4 5 For example, one study reported that the process of healing was sped up with the use of 20g of OKG. Wounds of burn patients who received OKG were healed in 60 days while the wounds of those without OKG were healed in 90 days. 6

To further understand this process, one study reported that 42 burn patients on day 7 post-burn, were randomly assigned to receive a single bolus of 10g of OKG given via enteral nutrition, or a continuous gastric infusion of 10, 20 or 30g OKG for 21 hours, or an isonitrogenous control. Researchers analyzed the plasma of these patients and reported that OKG was metabolized and produced glutamine, arginine and proline. These metabolites, which help regulate protein production, can be depleted one week after injury but with the inclusion of OKG, these levels can be increased to help patients heal from burns. 7

Surgery Patients

Surgery, trauma, and starvation can be stressful to the human body. These clinical states can decrease protein production and decrease free glutamine in the peripheral tissue, which in turn can decrease protein synthesis in the skeletal muscle. Researchers report that Total Parenteral Nutrition (TPN) does not stop this decrease but when TPN includes OKG or alpha-ketoglutarate, nitrogen balance improves and the loss of protein synthesis is not as pronounced. It is believed that since alpha-ketoglutarate is used to make glutamine, then this compound might be responsible for improving protein synthesis.

Researchers saw a similar action involving total hip replacement patients. Patients were divided into three groups. The control group received glucose, the next group received glutamine and the third group received alpha-ketoglutarate. Small samples of muscle were taken before and 24-hours after surgery. Researchers reported that free glutamine and protein synthesis were lowered among the control group but remained unchanged in the glutamine and alpha-ketoglutarate groups. 8

Patients undergoing elective gall bladder removal were given OKG, alpha-ketoglutarate, alanyl-glutamine or the basic TPN. Researchers noted that the group receiving basic TPN had a bigger drop in polyribosome concentration—a marker for protein synthesis, glutamine concentration in the skeletal muscle, and nitrogen balance. 9 And yet another study among elective abdominal surgery patients showed improvement in muscle glutamine when they were given OKG. 10

Other areas of study

OKG has been studied in other clinical conditions.

Cancer patients are known to lose weight and muscle. Some animal experiments involving cancer have shown that when OKG is given, protein breakdown decreases and other experiments have shown an increase in nitrogen retention. These results lead researchers to suspect that OKG may help maintain muscle mass in cancer patients.3

Other areas of study include compromised immune system in acute and chronic conditions, brain injury and growth. In these preliminary studies, OKG has been shown to influence growth among those with a compromised health status due to long-term diseases, and replenishing glutamine stores among rats who suffered from infection.3

The data for the effect of OKG on protein synthesis and nitrogen balance is substantial, but its effect on insulin and growth hormone is not as clear. Additional studies need to be conducted to further clarify the role of OKG on these hormones.

OKG in healthy subjects

The majority of studies involving OKG have been associated with clinical conditions. However there are studies that look at the role of OKG in healthy individuals.

Cynober and colleagues gave six fasting, healthy male subjects three separate oral load tests of 10g OKG, 6.4g of ornithine and 3.6g of alpha-ketoglutarate. Researchers drew blood 15 times during a five-hour period to measure plasma amino acids, alpha-ketoglutarate and glucagon. Plasma ornithine and OKG peaked at 60–75 minutes after administration of ornithine and OKG. Increase of plasma alpha-ketoglutarate was small but OKG, alpha-ketoglutarate and ornithine increased glutamate concentrations within 60 minutes. Only OKG increased proline and arginine within 60 minutes. This study shows that ornithine and alpha-ketoglutarate modifies protein metabolism in healthy individuals.11

Another human study evaluated OKG among healthy, weight trained men. Initially, 20 subjects were randomly assigned. The experimental group had 8 men (two dropped out in the fifth week for unknown reasons) and the control group had 10 men. Subjects performed the following for 6 weeks and were tested in 1-RM squat, 1-RM bench press, Wingate test, vertical jump, and underwater weight training at the beginning and end of the study. At the beginning, subjects fasted for 12 hours, and then received 75g of carbohydrate with either 10g OKG or a placebo. Blood samples were collected at baseline, 30, 60, and 90 minutes. Baseline dietary data were similar among both groups except the experimental group ate more carbohydrates. Other major nutrients and performance variables were similar for both groups during the study. The OKG group had a 6.6 percent increase in bench press strength and the control group had a 1.5 percent increase. This difference is statistically significant (p<0.05). No significant differences were noted in squat performance. OKG did not change training intensity or increase muscle mass. It did not change blood concentrations of insulin or growth hormone. It appears that OKG had an impact on bench press strength performance but not squat performance. Because of these differences, the performance of OKG among healthy, weight trained men shows great promise but remains unclear. Researchers need to examine this further to help define the role of OKG in healthy, weight trained men.12

Is OKG safe?

OKG has been taken in levels of 10g per day for as long as six weeks without reported side effects. The only side effect that has been reported is diarrhea in dosages above 15g per day.3 OKG has not been reported in scientific literature to negatively interact with other nutritional supplements or medications. It has been reported as a popular amino acid supplement among healthy individuals taken in recommended amounts without side effects.

OKG has had a wonderful journey through science and seems to be a great addition among healthy individuals who want to maintain muscle mass and/or to increase muscle mass; and among those who are challenged with clinical conditions involving muscle breakdown. Research has shown that in these individuals, OKG helps to lower protein breakdown in muscles, maintain protein production and keep nitrogen in balance. These functions are what help maintain muscle mass and keep muscles strong. Of course, other studies are needed to help uncover additional benefits of OKG. So whether you are young or old, challenged with clinical conditions or a little concerned about Sarcopenia, OKG can be an amazing addition to your supplement regimen.


  1. Cynober L. Ornithine að-ketoglutarate as a potent precursor of arginine and nitric oxide: a new job for an old friend. J Nutr. 2004 134:2858S-62S.
  2. Cynober L. Ornithine alpha-ketoglutarate in nutritional support. Nutrition. 1991 Sept-Oct;7(5):313-22.
  3. Rapport L, and Lockwood B. Ornithine Ketoglutarate. The Pharmaceutical Journal. 2001 May 19;266:688-90.
  4. Jeevanandam M, Petersen SR, Substrate fuel kinetics in enternally fed trauma patients supplemented with ornithine alpha ketoglutarate, Clin Nutr. 1999 Aug;18(4):209-17.
  5. Donati L, Ziegler F, Pongelli G, Signorini MS, Nutritional and clinical efficacy of ornithine alpha-ketoglutarate in severe burn patients, Clin Nutr. 1999 Oct;18(5):307-11.
  6. Coudray-Lucas C, Le Bever H, Cynober L, De Bandt JP, Carsin H, Ornithine alpha-ketoglutarate improves wound healing in severe burn patients: a prospective randomized double-blind trial versus isonitrogenous controls, Crit Care Med. 2000 Jun;28(6):1772-6.
  7. Le Bricon T, Coudray-Lucas C, Liret N, et al. Ornithine að-ketoglutarate metabolism after enteral administration in burn patients: bolus compared with continuous infusion. Am J Clin Nutr. 1997;65:512-8.
  8. Blomqvist BI, Hammarqvist F, von der Decken A, et al. Glutamine and alpha-ketoglutarate prevent the decrease in muscle free glutamine concentration and influence protein synthesis after total hip replacement. Metabolism. 1995 Sept;44(9):1215-22. PMID: 7666798.
  9. Vinnars E, Hammarqvist F, von der Decken A, et al. Role of glutamine and its analogs in posttraumatic muscle protein and amino acid metabolism. J Prenter Enteral Nutr. 1990 Jul-Aug;14(4 Suppl):125S-129S. PMID: 2119458.
  10. Wernerman J, Hammarkvist F, Ali MR, et al. Glutamine and ornithine-alpha-ketoglutarate but not branched-chain amino acids reduce the loss of muscle glutamine after surgical trauma. Metabolism. 1989 Aug;38(8 Suppl 1):63-6. PMID 2503684.
  11. Cynober L, Coudray-Lucas C, de Bandt JP, et al. Action of ornithine alpha-ketoglutarate, ornithine hydrochloride, and calcium alpha-ketoglutarate on plasma amino acid and hormonal patterns in healthy subjects. Journal of the Ammerican College of Nutrition. 1990; 9(1):2-12.
  12. Chetlin RD, Yeater RA, Ullrich IH, et al. The effect of ornithine alpha-ketoglutarate (Okg) on healthy, weight trained men. Journal of Exercise Physiology (online). 2000; 3(4).

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