Current issues of ACP Journal Club are published in Annals of Internal Medicine


Letter

Ornithine oxoglutarate improved nutrition in elderly patients

ACP J Club. 1995 Sept-Oct;123:56. doi:10.7326/ACPJC-1995-123-2-056



To the Editor

The commentary by Saltzman (1) on the article by Brocker and colleagues (2) suggested unwarranted cautions on the clinical applications of the outcomes. Saltzman indicated that ornithine oxoglutarate (OGO), which is popularly known as OKG (ornithine-α-ketoglutarate), is not safe. Saltzman is correct in stating that OGO is not approved by the U.S. Food and Drug Administration (FDA), but this is only for parenteral use. FDA approval is not required for oral use, the form in this study, because the components of this compound are natural metabolites of the body and have no proven toxic or lethal side effects. OGO is currently available in most health food stores in the United States and is used in European countries for both oral and parenteral administration.

Saltzman raised the issue of the exact mechanism of action of OGO, which was not the primary objective or aim of this clinical study. Recently, Cynober (3) concluded that the actions of OGO result from the effects of the combination of ornithine and α-ketoglutarate and depend on anabolic hormone secretion (growth hormone, insulin-like growth factor type 1, and insulin) and possibly the synthesis of metabolites that control protein metabolism. This is appropriately discussed by Brocker and colleagues (2).

Saltzman also questioned the cause of weight gain. Brocker and colleagues reported a significant (P < 0.001) increase in body weight caused by 30 days of OGO treatment and 30 days of convalescence without OGO. Although the investigators did not keep an accurate record of food intake, they observed an increase (P < 0.001) in the appetite for meat and an increase in physical activity in the elderly patients who were followed. The improvements seen in protein metabolism (2-4) appear to indicate that OGO treatment would add more muscle than fat or water.

In the dose given, OGO was effective in preventing secondary malnutrition after intercurrent illnesses in independently living elderly persons after acute illness. As pointed out by the authors (2), the improvements concerned not only subjective indices but also objective nutritional markers. Oral OGO at 10 g/d seems to be safe and cost-effective and to have measurable clinical improvements. Long-term use of oral OGO in treating elderly persons in the United States should be encouraged.

Malayappa Jeevanandam, PhD
St. Joseph's Hospital and Medical Center
Phoenix, Arizona, USA

In response

Dr. Jeevanandam raises several issues in the commentary that I wrote (1) for the article by Brocker and colleagues (2) that deserve clarification. Ornithine has well-known deleterious effects on water and electrolyte transport because it stimulates net secretion at high concentrations. Oral administration of OGO has been observed to cause diarrhea at doses slightly higher (> 15 g/d) (3) than that used in the study by Brocker and colleagues. I think clinicians should be aware of this side effect of OGO because patients considered for supplementation may not closely resemble those who participated in previous trials. In addition, 5 of the 6 patients excluded from analysis in the OGO treatment group were excluded because of diarrhea.

I believe that better information about the cause of the weight gain would be clinically useful to determine whether added muscle, fat, or water was responsible for the observed changes. Although an increase in appetite for meat and an increase in physical activity would be consistent with added muscle, a direct measurement of muscle protein would be more accurate. Brachial circumference was measured in this study (a measure of lean body or skeletal mass), but no significant improvement was seen in the OGO group.

As mentioned in my commentary, the study by Brocker and colleagues is well done and is an important contribution to the literature of nutritional management of elderly persons. OGO supplementation is a potentially important addition to other nutritional interventions in elderly persons. Before widespread supplementation can be encouraged, further studies should be done to determine its efficacy and safety.

John R. Saltzman, MD
University of Massachusetts Medical Center
Worcester, Massachusetts, USA


References

1. Saltzman JR. Commentary on “Ornithine oxoglutarate improved nutritional status in elderly patients after hospital discharge” ACP J Club. 1995 Jan-Feb;122:16. Comment on: Brocker P, Vallas B, Albarede Al, Poynard T. Age Ageing. 1994;23:303-6.

2. Brocker P, Vellas B, Albarede JL, Poynard T. A two-centre, randomized double-blind trial of ornithine oxoglutarate in 194 elderly, ambulatory, convalescent subjects. Age Ageing. 1994;23:303-6.

3. Cynober L. Ornithine alpha-ketoglutarate in nutritional support. Nutrition. 1991;7:313-22.

4. Jeevanandam M. Ornithine and ketoglutarate in trauma. Clinical Nutrition. 1993;12:61-2.

1. Saltzman JR. Commentary on “Ornithine oxoglutarate improved nutrition in elderly patients.” ACP J Club. 1995 Jan-Feb;122:16. Comment on: Brocker P, Vallas B, Albarede Al, Poynard T. A two centre, randomized double-blind trial of ornithine oxoglutarate in 194 elderly ambulatory convalescent subjects. Age Ageing. 1994;23:303-6.

2. Brocker P, Vellas B, Albarede JL, Poynard T. A two-centre, randomized double-blind trial of ornithine oxoglutarate in 194 elderly, ambulatory, convalescent subjects. Age Ageing. 1994;23:303-6.

3. Cynober L. Ornithine alphaketoglutarate in nutritional support. Nutrition. 1991; 7:313-22.